ORGANIC   CHEMISTRY 

FOR 

ADVANCED   STUDENTS 


ORGANIC  CHEMISTRY 

FOR 

ADVANCED  STUDENTS 


PART  I 
REACTIONS 


BY 

JULIUS   B.  COHEN,  PH.D.,  B.Sc.,  F.R.S. 

PROFESSOR  OF  ORGANIC  CHEMISTRY  IX  THE  UXIVERSITY  OF  LEEDS 


SECOND   EDITION 
SECOND   IMPRESSION 


NEW  YORK 

LONGMANS,  GREEN  &  CO, 

LONDON  :   EDWARD  ARNOLD 
1919 

[All  rights  reserved \ 


PREFACE  TO   THE  SECOND   EDITION 

THE  object  of  recasting  the  former  two  volumes  of  the 
'  Organic  Chemistry  for  Advanced  Students '  in  the  three  parts 
in  which  they  now  appear  has  been  to  group  together  allied 
subjects  and  to  link  them  as  far  as  possible  in  a  consecutive  form. 
As  this  entailed  re-arrangement  of  the  plates,  an  opportunity 
was  afforded  of  bringing  the  subject-matter  up  to  date,  and 
very  considerable  additions  have  been  made  to  the  contents 
of  the  former  volumes.  As  stated  in  the  original  preface, 
the  book  is  not  intended  to  serve  as  a  reference  book,  but  to 
furnish  a  general  survey  of  those  fundamental  principles  which 
underlie  the  modern  developments  of  this  branch  of  chemistry. 

J.  B.  COHEN. 
March,  1918. 


•J 


CONTENTS 

PART  I 
CHAPTER  I 

PAGE 

HISTORICAL  INTRODUCTION         .......        1 

CHAPTER  II 

VALENCY  OP  CARBON 56 

Variable  Valency,  56,  57.  Tervalent  Carbon,  59.  Triphenylmetbyl, 
60  ;  Bivalent  Carbori,  65.  -Structure  of  Isocyanides,  66.  Metallic 
Cyanides,  67.  Fulminic  Acid,  71.  Acetylene  Compounds,  73.  Theory 
of  the  Double  Bond,  74.  Theory  of  Free  Valencies,  77.  Theories  of 
Valency  (Werner,  Fliirscheim,  Tschitschibabin,  Wunderlich),  83. 
Electrochemical  Theories  (J.  J.  Thomson,  Stark,  Abegg  and 
Bodlander,  Briggs),  97. 

CHAPTER  III 

NATURE  OF  ORGANIC  REACTIONS          .         .  .         .         .107 

Valency  and  Affinity,  107.  Types  of  Reactions,  109.  Addition,  111. 
Autoxidation,  121.  fhe  Ketenes  ;  Carbon  Suboxide,  129.  Thiele's 
Theory,  133.  Substitution  in  the  Aromatic  Series,  149.  Theories 
of  Substitution,  153.  Catalytic  Reactions  (reduction,  dehydro- 
genation,  dehydration,  oxidation,  ralogenation,  condensation, 
polymerisation),  162.  Chain  and-Ring  Formation,  Condensation, 
174.  Baeyer's  Strain  Theory,  178.  Ring  Structures,  179.  Con- 
densation, by  separation  of  elements  (Method  of  Wurtz,  Wislicenus, 
Perkin,  Reiiner-Tiemann,  Friedel-Crafts,  Ullmann),  187 ;  by  re- 
moval of  Carbon  Dioxide,  200.  Additive  Reactions  (Method  of 
Michael,  Buchner-Curtius,  Frankland,Grignard,Reformatsky),  201. 
Acetoacetic  Ester  Method,  220.  Aldol  Condensation,  237.  Re- 
action of  Claisen,  238 ;  Knoevenagel,  241.  Benzoin  Condensa- 
tion, 245.  Pinacone  Condensation,  246.  Reaction  of  Perkin,  248  ; 
Thorpe,  252.  Carbon-nitrogen  Chain  and  Ring  Formation,  254. 
Carbon-oxygen  Chain  and  Ring  Formation,  258. 


viii  CONTENTS 

CHAPTER  IV 

PAGE 

DYNAMICS  OF  ORGANIC  REACTIONS 275 

Law  of  Mass  Action,  275.  Unimolecular  Non-reversible  Reactions, 
277.  Polymolecular  Non-reversible  Actions,  279.  Bimolecular 
Reactions,  279.  Termolecular  Reactions,  281.  Determination  of 
the  Order  of  a  Reaction  (Velocity  coefficient  method,  initial 
velocity  method,  method  of  equifractional  parts,  isolation  method), 
282.  Stereo-chemical  Changes,  285.  Isomeric  Changes,  286. 
Hydrolysis  of  Sugars,  287.  Esterifi cation,  290.  Decomposition  of 
Diazo-compounds,  293.  Frie del-Crafts  Reaction,  297.  Concurrent 
Reactions,  299.  Substitution,  305.  Reversible  Reactions,  306. 
Dynamic  Isomerism,  308.  Mutarotation,  310.  Consecutive  Re- 
actions, 314.  Action  of  Halogens  on  Ketones,  318.  Oxidation  of 
Alcohol,  321.  Photo-chemical  Reactions,  322.  Catalysed  Reactions, 
326.  Heterogeneous  Reactions,  328. 

CHAPTER  V 

ABNORMAL  REACTIONS        ........    330 

Steric  Hindrance,  330.  Victor  Meyer's  Esterification  Law,  334. 
Esterification  Law  applied  to  Fatty  Acids,  340.  Hydrolysis  of 
Esters,  343  ;  of  Amides  and  Acyl  Chlorides,  344  ;  of  Cyanides,  345. 
Action  of  Alcohols  on  Acid  Chlorides,  346.  Formation  of  Alkyl 
Ammonium  Iodides,  346.  Alkylation  of  Bases  and  Phenols,  347. 
Acetylation  of  Secondary  Bases,  347.  Reactions  of  Phenyl- 
hydroxylamine,  348.  Action  of  Benzaldehydes  on  Amines,  348 ; 
of  Aldehydes  on  Pyridine  Bases,  349.  Formation  of  Rosanilines, 
349.  Action  of  Phosphorus  Pentachloride  on  Hydroxy-acids,  350. 
Reduction  of  Nitro  Compounds,  350.  Chain  Formation,  350. 
Bisch off 's  Theory,  351. 

INDEX  OF  SUBJECTS 355 

INDEX  OF  AUTHORS 362 


ORGANIC   CHEMISTRY 

PAET    I 
CHAPTEE  I 

HISTOKICAL  INTRODUCTION 

The  Radical1  of  Benzole  Acid.  In  the  year  1832  Liebig  and 
Wtfhler  published  their  classical  memoir,  entitled,  '  Experiments  on 
the  Radical  of  Benzoic  Acid  '.* 

Viewed  in  the  light  of  our  present  knowledge  there  is  nothing 
very  remarkable  in  the  facts  which  they  discovered.  Starting  with 
bitter  almond  oil,  which  we  now  term  bensaldehyde,  they  converted 
it  by  the  action  of  chlorine  and  bromine  into  benzoyl  chloride  and 
bromide.  Benzoyl  chloride  treated  successively  with  potassium 
iodide  gave  benzoyl  iodide ;  with  ammonia,  benzamide  ;  with  lead 
sulphide,  benzoyl  sulphide ;  with  mercuric  cyanide,  benzoyl  cyanide 
and  with  alcohol,  benzoic  ether.  Bitter  almond  oil  had,  moreover, 
been  found  by  Stange  (1824)  to  undergo  rapid  oxidation  in  the  air 
and  to  be  transformed  into  an  acid— benzoic  acid — identical  with 
the  substance  derived  from  gum  benzoin. 

Such  is  briefly  the  substance  of  the  investigation  to  which  the 
following  introduction  is  attached.  'When  a  chemist  is  fortunate 
enough  to  perceive  one  ray  of  light  penetrating  the  dark  region  of 
organic  nature,  which  may  mark  the  entrance  to  the  right  path 
of  future  knowledge,  he  has  reason  to  feel  encouraged,  although 
conscious  of  the  vastness  of  the  field  which  lies  before  him.' 

In  order  to  realize  the  importance  of  a  memoir  which  created 
a  profound  impression  among  contemporary  chemists,  and  was 
welcomed  by  Berzelius  as  '  the  dawn  of  a  new  day ',  we  must  take 
a  glance  at  the  branch  of  chemistry  which  at  this  period  formed 
1  the  dark  region  of  organic  nature '. 

Origin  of  the  Radical  Theory.  If  we  turn  to  Lemery's  Cbttra 
de  Chymie,  which  was  the  popular  text-book  from  1675  down  to  the 
middle  of  the  eighteenth  century,  we  find  all  known  substances 

1  It  is  an  interesting  and  curious  fact  that  with  admittedly  'little  to  recom- 
mend it'  (Trans.  Chem.  Soc.,  1905,  87,  548)  the  Chemical  Society  of  Great  Britain 
has  seen  fit  to  alter  the  original  spelling  to  *  radicle ',  and  the  Society  now  holds 
the  unique  position  of  being  the  only  representative  body  of  chemists  which 
has  adopted  this  spelling. 

a  Liebig's  Annalen,  1832,  3,  249  ;  Ostwald's  Klassiker,  No.  22. 

PT.  I  B 


^ORGANIC  CHEMISTRY 

distributed  according  ^  their  origin  between  the  mineral,  vegetable 
and  animal  kingdoms.  Under  the  two  divisions  of  vegetables  and 
animals  occur  the  names  of  substances  which  have  been  known 
from  remote  times,  such  as  sugar,  starch,  fats  and  oils,  gums  and 
resins.  By  the  process  of  distillation  alcohol  had  been  obtained 
from  fermented  liquids,  acetic  acid  from  vinegar,  turpentine  from 
resin,  and  various  sweet  scented  oils  from  plants.  Vegetable 
colouring  matters  were  employed  in  dyeing,  and  oils  and  fats  in  the 
production  of  soap.  Extracts  of  cinchona  bark,  opium  and  other 
vegetable  substances  were  used  in  medicine.  Towards  the  close  of 
the  eighteenth  century  Scheele  isolated  and  clearly  distinguished  the 
acid  principles  present  in  various  vegetable  and  animal  products. 
He  found  malic  acid  in  apples,  citric  acid  in  lemons,  oxalic  acid  in 
wood  sorrel,  gallic  acid  in  galls,  lactic  acid  in  sour  milk,  and  uric 
acid  in  urine.  He  also  obtained  from  olive  oil,  by  boiling  it  with 
lead  oxide,  a  sweet,  viscid  liquid,  which  we  now  know  as  glycerine. 

These  varied  products  of  animal  and  plant  life  which,  when 
ignited  took  fire,  or  when  heated  in  closed  vessels  charred  and  gave 
off  water  and  other  volatile  matters,  contained,  according  to  the 
views  of  the  phlogistonists,  more  of  the  aqueous  and  combustible 
principle  or  phlogiston,  than  mineral  substances.  They  were  termed 
organic  to  indicate  their  origin  from  living  or  organized  matter. 

With  Lavoisier's  discovery  of  the  cause  of  oxidation  and  com- 
bustion, the  element  oxygen  became  in  chemistry  very  much  what 
the  sun  is  in  our  solar  system.  The  chemistry  of  Lavoisier  was  the 
chemistry  of  oxygen.  All  compounds  were  oxides,  generally  simple 
oxides  of  another  element.  To  the  other  element  attached  to  oxygen 
de  Morveau  applied  the  term  base  or  radical.  The  simple  oxides 
were  divided  into  salifiable  and  acidifiable  bases,  and  these  united 
to  form  salts.1  The  system  was  essentially  dualistic,  and  con- 
tained the  germ  of  the  theory  subsequently  developed  by  Berzelius. 
Lavoisier,  who  was  the  first  to  demonstrate  the  true  composition  of 
organic  substances,  extended  the  idea  of  radical  so  as  to  embrace 
these  compounds  (1784).  Organic  substances  which  generally  con- 
tained carbon,  hydrogen,  and  oxygen,  and  occasionally  nitrogen  and 
phosphorus,  were  regarded  as  oxides  of  a  radical,  composed  of  at 
least  two  elements,  carbon  and  hydrogen.  Sugar,,  which  yielded 
oxalic  acid  on  oxidation,  was  the  oxide  of  a  hydrocarbon  radical,  and 
oxalic  acid  formed  its  higher  oxide.  The  radical  tvas  purely  hypo- 
thetical Indeed,  so  little  was  then  known  about  the  nature  of 
organic  compounds  that,  with  the  advent  of  the  atomic  theory, 
1  Lavoisier's  Elements  of  Chemistry,  translated  by  Kerr,  1802, 1,  289. 


ORIGIN  OF  THE  RADICAL  THEORY  3 

it  was  held  to  be  doubtful  if  the  elements  composing  them  com- 
bined in  simple  atomic  proportion  and  obeyed  the  laws  of  combina- 
tion which  had  been  found  to  obtain  in  the  province  of  inorganic 
chemistry.  Organic  compounds  were  the  products  of  a  vital  force, 
not  necessarily  dependent  on  the  chemical  laws  governing  inert 
matter.  This  view  was  commonly  held  until  Berzelius,  in  1814,  by 
improving  the  method  of  organic  analysis,  showed  from  the  results 
of  his  analyses  of  sugar  and  some  of  the  organic  acids,  that  organic 
compounds  were  subject  to  the  ordinary  laws  of  chemical  combination. 

Berzelius  adopted  Lavoisier's  view  of  the  nature  of  organic  com- 
pounds ;  for  in  his  Treatise  on  Chemistry  (2nd  edition),  published  in 
1817,  he  says :  'After  having  become  more  closely  acquainted  with 
the  difference  between  the  products  of  organic  and  inorganic  Nature 
and  the  different  manner  in  which  their  constituents  are  combined 
together,  we  have  found  the  difference  to  consist  in  this:  that  in 
inorganic  Nature  all  oxidised  bodies  possess  a  simple  radical,  whilst 
all  organic  substances  consist  of  oxides  of  compound  radicals.  In 
vegetable  substances  the  radical  consists  usually  of  carbon  and  hydro- 
gen, and  in  animal  products  of  carbon,  hydrogen,  and  nitrogen.' 

To  follow  the  history  of  organic  chemistry  from  this  point,  and  to 
realize  the  network  of  difficulties  in  which  its  votaries  became 
gradually  and  unconsciously  entangled,  it  will  be  necessary  to 
understand  the  electro-chemical  system  of  Berzelius  and  the  method 
of  notation  which  was  founded  upon  it. 

The  Atomic  and  Molecular  Weights  of  Berzelius.  The  dis- 
covery, in  1808,  of  Gay  Lussac's  law  governing  gaseous  combination 
or  the  '  law  of  volumes ',  as  it  was  commonly  called,  of  Dulong  and 
Petit's  law  (1819)  which  determined  the  relation  of  specific  heats  to 
the  combining  weights  of  the  elements,  and  of  Mitscherlich's  law  of 
isomorphism  (1820)  enabled  Berzelius,  after  a  careful  revision  of  the 
combining  proportions  of  the  elements,  to  assign  atomic  weights 
based  upon  principles  which  we  still  recognize  and  adopt.  Thus,  if 
equal  volumes  of  elementary  gases  contain  the  same  number  of 
atoms,  the  formula  for  water  must  be  represented  by  H20  since  two 
volumes  of  hydrogen  unite  with  one  volume  of  oxygen ;  NH3  will 
stand  for  ammonia,  and  HC1  for  hydrochloric  acid.  The  method  did 
not  involve  any  question  as  to  the  volumes  occupied  by  the  com- 
bined gas,  which  offered  a  difficulty  only  solved  later  when 
Avogadro's  distinction  of  molecules  constituantes,  and  integrantes,  or, 
as  we  now  say,  atoms  and  molecules,  was  clearly  recognized.1  The 

1  Die  Grundlagen  der  Mdekulartheorie,  Ostwald's  Klassiker,  No.  8  ;  Atogadro  and 
Dalton,  by  A.  N.  Meldrum,  pub.  \V.  F.  Clay,  Edin. 

B3 


ORGANIC  CHEMISTRY 


direct  application  of  the  law  of  volumes  was  limited  to  comparatively 
few  elements.  A  wider  range  of  atomic  weights  was  derived  from 
the  specific  heats  of  the  metals  and  the  isomorphism  of  their  salts. 
Where  none  of  these  principles  could  be  applied  the  atomic  weights 
were  ascertained  by  the  simplest  gravimetric  relation  of  an  element 
to  oxygen  in  its  oxide.  The  atomic  weights  of  the  metals  which 
formed  basic  oxides  were  derived  from  these  oxides  which  were 
assumed  to  contain  a  single  atom  of  each  element.  Consequently 
the  atomic  weights  of  the  alkali  metals  and  of  silver  which  formed 
isomorphous  salts  with  them,  received  double  their  present  values. 
The  formulae  for  potassium  and  silver  oxide  and  chloride  were 
written  KO,  KC12,  AgO,  AgCl2  ;  the  formulae  of  ammonia  and 
hydrochloric  acid,  originally  written  NH3  and  HC1,  were  afterwards 
doubled  by  using  the  barred  or  double  atom  thus  :  NH3  =  N2H6  and 
SCI  =  H2C12  with  the  object  of  making  them  equivalent  to  the 
atomic  weights  of  the  metals.  For  the  same  reason  H2  was  the 
equivalent  of  1  atom  of  oxygen  and  the  formula  for  water  appeared 
as  HO  =  H20. 

The  series  of  atomic  weights  elaborated  by  Berzelius  with  rare 
analytical  skill  and  an  unerring  instinct,  which  guided  him  where 
principles  failed,  differ  little  from  the  modern  values. 

In  the  third  column  of  the  following  table  is  a  list  of  the  more 
important  atomic  weights  taken  from  Berzelius'  revised  numbers, 
which  appeared  in  1826,  oxygen  being  100.  The  fourth  column 
contains  the  figures  calculated  with  hydrogen  as  the  unit ;  in  the 
fifth  column  are  the  present  values : 


Name. 

Formula. 

Berzelius'  i 
0=  100 

lumbers. 
H  =  l 

Present 
numbers. 
H  =  l 

Oxygen 

O 

100 

16-026 

15-88 

Hydrogen 

H 

6-239 

1-000 

1.00 

Nitrogen 

N 

88-518 

14-186 

13-93 

Sulphur 

S 

201.165 

32-239 

31.83 

Phosphorus 

P 

196.155 

31-436 

80-77 

Chlorine 

Cl 

221-325 

35-470 

35-18 

Iodine 

I 

768-781 

123-206 

125-90 

Fluorine 

F 

116-900 

18-734 

18-90 

Carbon 

C 

76-437 

12-250 

11-91 

Potassium 

K 

489-916 

78-515 

38-86 

Sodium 

Na 

290-897 

46-620 

22-88 

Silver 

Ag 

1351-607 

216.611 

107.12 

Calcium 

Ca 

256-019 

41-030 

39-80 

Strontium 

Sr 

547-285 

87.709 

86-94 

Barium 

Ba 

856-880 

137-325 

136-40 

Iron 

Fe 

339-213 

54-363 

55-50 

Aluminium 

Al 

171-167 

27-431 

26-90 

Chromium 

Cr 

351-819 

56-383 

51.70 

ATOMIC  AND  MOLECULAR  WEIGHTS  OF  BERZELIUS  5 

In  a  memoir  published  in  1826,  '  Sur  quelques  points  de  la  theorie 
atomistique,'  Dumas1  attempted  to  extend  the  application  of  Avo- 
gadro's  hypothesis  to  the  determination  of  both  atomic  and  molecular 
weights  from  the  densities  of  gases  and  vapours,  in  connection  with 
which  he  devised  his  well-known  method.  It  is  a  curious  fact  that 
he  not  only  failed  to  commend  his  method  to  the  chemical  world, 
but  ended  by  convincing  himself  of  its  futility. 

The  result  was  due  partly  to  a  clumsy  way  of  presenting  his  ideas, 
and  partly  to  the  confusion  introduced  by  the  anomalous  vapour 
densities  of  some  of  the  elements.  Dumas  set  forth  that  equal 
volumes  contain  the  same  number  of  atoms  or  molecules  ;  conse- 
quently, if  one  volume  or  atom  of  hydrogen  unites  with  one  volume 
or  atom  of  chlorine  to  form  two  volumes  or  atoms  of  hydrochloric 
acid,  the  original  atoms  of  hydrogen  and  chlorine  are  divisible 
into  half  atoms  of  each  element.  A  half  atom  of  oxygen  must 
for  the  same  reason  be  present  in  the  atom  of  water  and  so  forth. 
Though  Dumas,  no  doubt,  clearly  distinguished  between  his 
physical  atoms  or  molecules  and  his  chemical  or  half  atoms,  the 
subdivision  of  the  atom  implied  a  contradiction  in  the  term  and  did 
not  fail  to  call  forth  criticism.  As  Dalton  said,  '  No  man  can  split 
an  atom.' 2 

But  this  was  not  all.  Dumas'  atomic  weight  for  silicon, 
which  he  correctly  interpreted  from  the  vapour  density  of  the 
chloride,  differed  from  the  number  obtained  by  Berzelius,  who 
derived  it  from  the  oxide,  written  Si03  from  its  analogy  with  S03, 
CrO3,  &c.  The  atomic  weight  of  mercury,  determined  from  the 
vapour  density  of  the  metal,  was  half  that  assigned  by  Berzelius 
from  its  specific  heat.  Finally,  the  anomalous  vapour  densities  of 
phosphorus,  sulphur,  and,  as  Mitscherlich  found  later,  arsenic, 
gave  atomic  weights  which  conflicted  with  those  previously  derived 
by  Dumas  himself  from  the  vapour  densities  of  their  hydrides  and 
chlorides  and  shook  his  confidence  in  his  own  method. 

Berzelius'  system  of  atomic  weights  also  had  its  critics.  As  we 
have  seen,  doubt  had  been  thrown  by  Dumas  on  the  validity  of 
the  law  of  volumes.  The  atomic  weights  of  several  of  the  elements 
which  were  derived  from  the  specific  heats  did  not  conform  to  the 
atomic  weights  deduced  from  the  law  of  isomorphism  ;  for  example, 
the  isomorphism  of  the  silver  salts  and  those  of  the  alkalis  fixed 
the  atom  of  silver  at  216,  whilst  its  specific  heat  gave  the  number 
108.  Mitscherlich's  law  itself  was  not  free  from  objection,  inasmuch 

1  Ann.  Ohim.  Phys.,  1826,  33,  337. 

2  Memoirs  of  Dalton,  by  Dr.  Henry. 


6  ORGANIC  CHEMISTRY 

as  the  existence  of  dimorphous  substances  left  the  choice  in  some 
cases  doubtful. 

The  principles  which  served  Berzelius  for  his  determinations 
gradually  fell  into  discredit. 

Gmelin's  Equivalents.  Leopold  Gmelin,  the  author  of  the 
classical  treatise  which  bears  his  name,  suggested  a  reversion  to 
the  system  of  equivalents,  a  term  introduced  by  Wollaston  in  1808. 
It  represented  the  simplest  gravimetric  relations,  without  reference 
to  the  law  of  volumes,  and  received  strong  support  from  Faraday's 
newly  discovered  electrolytic  law  (1832). 

The  old  and  new  systems  were  easily  reconciled  by  using  the 
barred  or  double  atom  of  Berzelius,  and  appeared  side  by  side  for 
many  years  without  giving  rise  to  confusion,  until  the  double  atom 
eventually  disappeared.  Kolbe  was  one  of  the  last  to  use  the 
barred  atom  of  Berzelius,  which  he  abandoned  about  1850  in  favour 
of  the  equivalent  notation. 

The  following  formulae  for  water,  hydrochloric  acid,  ammonia, 
and  phosphoric  oxide,  represent  the  original  and  modified  notation 
of  Berzelius  and  the  corresponding  equivalent  notation  of  Gmelin : 

Berzelius  (  original  formula  H20  H2C12  N2H6  P205 

(H  =  1 ;  O  =  16)  ( modified  „  HO  B£l  #S3  £05 

Gmelin  equivalent  „  HO  HC1  NH3  P06 

(H  =  1 ;  0  =  8) 

Henceforth,  densities  of  volatile  organic  compounds,  though 
frequently  determined  with  the  object  of  controlling  analytical 
results,  never  served  as  a  means  of  ascertaining  molecular  weights 
until  many  years  had  elapsed,  when  Gerhardt  and  Laurent  revived 
the  hypothesis  of  Avogadro  and  Ampere.  The  aggregate  weight 
of  the  atoms  might  correspond  to  one,  two,  or  a  multiple  of  two 
volumes  of  the  vapour  compared  with  one  volume  of  hydrogen. 

The  formulae  for  chloral  C4C16H2O2,  chloroformC2H.>Cl6,  alcohol 
C4H1202,  and  acetic  ether  C8H1604,  corresponded  to  four  volumes, 
whereas  those  for  ether  C4H10O,  oxalic  ether  C6H10O4,  and  succinic 
ether  C8H14O4,  corresponded  to  only  two  volumes.  It  was  left  to  the 
choice  of  the  investigator  to  select  an  appropriate  molecular  formula. 
We  shall  presently  see  how  the  confusion,  which  arose  from  the 
absence  of  any  recognized  method  for  fixing  molecular  weights, 
resulted  in  many  a  fruitless  and  embittered  controversy. 

Berzelius'  Electro-chemical  Theory.  The  electro-chemical  theory 
of  Berzelius  (1819)  dominated  chemistry  during  the  first  third  of  the 


BERZELIUS'  ELECTRO-CHEMICAL  THEORY  7 

last  century.  Carefully  elaborated  in  the  case  of  inorganic  compounds, 
it  was  sought  to  apply  it  in  the  same  comprehensive  manner  to 
organic  compounds.  It  was  the  guiding  principle  to  which  Berzelius 
clung  throughout  his  life.  But  the  young  and  rapidly  growing 
branch  of  the  science  was  not  to  be  crippled  by  an  artificial  system 
which  arrested  its  natural  development.  After  a  fierce  controversy 
between  Berzelius  and  the  chemists  of  the  French  school  the  theoiy  was 
finally  abandoned.  The  theory  may  be  briefly  defined  as  Lavoisier's 
dualistic  views  expressed  in  the  light  of  Davy's  and  Berzelius'  electro- 
chemical researches.  Each  atom  of  the  elements  was  supposed  to 
possess  opposite  electrical  poles  provided  with  different  quantities  of 
electricity,  so  that  it  contained  a  surplus  of  one  or  other  kind  of 
electricity,  and  was  either  positive  or  negative  according  to  the 
predominating  polarity.  It  was  by  virtue  of  their  opposite  polarities 
that  the  atoms  combined.  The  simple  combinations  of  positive  and 
negative  elements  furnished  compounds  of  the  first  order.  The  elec- 
tricities in  these  compounds  were  not  necessarily  neutralized,  and 
there  might  still  remain  a  surplus  positive  or  negative  charge  which 
enabled  them  to  enter  into  further  combinations,  forming  compounds 
of  the  second  order.  The  elements  were  arranged  in  electrical  series 
with  oxygen  at  one  end,  representing  the  most  electro-negative 
element,  and  the  alkali  metals  at  the  other,  representing  the  most 
electro-positive  elements.  Each  intermediate  element  would  be 
electro-positive  to  the  one  that  preceded  and  electro-negative  to 
that  which  followed.  The  metals  were  strongly,  the  non-metals 
weakly  electro-positive  towards  oxygen.  The  lower  metallic  oxides 
retained,  therefore,  a  residual  positive,  the  non-metallic  oxides  a 
residual  negative  polarity.  Thus  potash  KO  was  electro-positive, 
whilst  sulphuric  acid  SO3  was  electro-negative.  Potash  and  sulphuric 
acid  could  therefore  combine,  by  virtue  of  their  opposite  polarities,  to 
form  sulphate  of  potash,  which  was  written  SO3  +  KO.  The  elec- 
tricities might  still  remain  unneutralized,  and  by  the  formation  of 
double  salts  such  as  potash  alum,  compounds  of  the  third  order  were 
obtained. 

The  oxides  of  the  non-metals  were  called  acids;  N2O5  stood  for 
nitric  acid  and  N205  +  H2O  was  its  hydrate.  When  the  combined 
water  of  the  hydrate  or  "basic  ivater  was  replaced  by  a  metallic  oxide 
or  base,  a  neutral  salt  resulted.  The  same  principle  was  applied  to 
organic  acids  and  their  salts.  Acetic  acid  was  written  C4H603  and 
its  hydrate  (our  acid)  C4H603  +  JLO ;  C203  stood  for  oxalic  acid,  and 
the  crystalline  compound  which  we  now  term  anhydrous  oxalic  acid 
C2O3  +  H20  was  regarded  as  its  hydrate;  benzoic  acid  was  C14H1003  and 


8  ORGANIC  CHEMISTRY 

its  hydrate  (our  acid)  was  C14H10O3  +  H2O.  The  molecular  formula  for 
the  acids  was  derived  from  the  composition  of  the  salts,  usually  the 
silver  salts,  and  as  all  salts  were  supposed  to  contain  one  atom  of  base 
(silver  and  the  alkalis  had  double  their  present  atomic  weights),  it 
necessarily  followed  that  all  monobasic  acids,  like  acetic  and  benzoic, 
had  double  their  present  formulae,  whereas  dibasic  acids  received 
their  modern  values.  It  should  be  observed  that  these  so-called 
organic  acids  only  existed  in  the  form  of  their  hydrates,  the  acids 
themselves  being  purely  fictitious  groups  of  elements, 

Organic  Chemistry  in  1830.  In  1830  Liebig  introduced  his 
new  method  of  organic  analysis,  which  is  essentially  the  one  we  still 
employ.1  There  is  no  doubt  that  the  simplicity  and  rapidity  of  this 
process  gave  a  new  impulse  to  the  study  of  organic  chemistry.  To 
perform  an  organic  analysis  appears  to  have  been  a  troublesome 
business,  for  in  a  letter  from  Wohler  to  Liebig  written  in  August, 
1830,  we  read :  '  A  thousand  thanks  for  your  quick  reply.  To  be 
able  to  complete  an  analysis  so  rapidly  is  scarcely  within  the  power 
of  any  one  but  yourself,  certainly  not  in  mine,  for  I  have  a  whole- 
some dread  of  doing  one.' 

Organic  chemistry  in  1830  embraced  a  large  number  of  substances 
of  widely  different  properties,  yet  composed  usually  of  only  three  or 
four  elements — carbon,  hydrogen,  oxygen,  and  nitrogen.  It  included 
a  variety  of  organic  acids  and  a  steadily  increasing  number  of  organic 
bases  or  alkaloids,  the  first  of  which — morphium — had  been  isolated 
in  1817  by  Serturner  from  opium ;  also  a  number  of  indifferent  sub- 
stances— hydrocarbons,  spirits  of  wine,  sugar,  starch,  gums — and 
finally,  the  fats  and  fixed  oils,  the  composition  of  which  had  been 
studied  by  Chevreul  in  so  complete  and  masterly  a  fashion  that  our 
knowledge  of  these  substances  has  not  materially  advanced  since  his 
day.  He  showed  that  these  bodies  were  compounds  of  glycerine  with 
various  acids  (the  fatty  acids)  and  that  they  behaved  like  acetic  ether, 
decomposing  with  alkalis  into  the  salt  of  the  acid  and  glycerine. 
There  was,  however,  little  analogy  between  the  complexity  of  all 
these  bodies  and  the  simple  compounds  of  inorganic  chemistry,  in 
which  one  element  united  with  another  in  one  or  two,  more  rarely 
in  three,  proportions.  Berzelius2  at  first  distinguished  inorganic 
compounds  as  binary,  that  is  to  say,  divisible  and  sub-divisible  into 
two  parts,  one  electro-positive  and  the  other  electro-negative,  whilst 
organic  compounds  contained  more  than  two  elements  which  were 

1  Berzelius,  Jahresb.,  1831,  11,  214 ;  Pogg.,  Ann.,  1831,  21,  1. 
*  Ann.  Phil.,  4,  323. 


ORGANIC  CHEMISTRY  IN  1830  9 

directly  combined  into  a  whole  and  could  not  be  subdivided  or 
reunited  after  the  manner  of  inorganic  compounds.  Hydrocarbons 
like  marsh  gas  and  turpentine,  since  they  contained  only  two 
elements,  were  consequently  classed  among  inorganic  compounds, 
and  occur  under  this  head  in  the  earlier  numbers  of  Berzelius' 
Jahresbericht.  But  this  distinction  was  not  long  maintained.  Or- 
ganic chemistry  was  still  essentially  the  chemistry  of  animal  and 
plant  products  and  their  derivatives.  It  is  true  that  from  time  to 
time  the  artificial  production  of  natural  substances  was  announced. 
As  far  back  as  1776  Scheele  had  obtained  oxalic  acid  identical  with 
that  in  wood  sorrel  by  the  oxidation  of  sugar  with  nitric  acid.  In 
1822  Dobereiner  had  prepared  formic  acid,  hitherto  obtained  by  the 
distillation  of  ants,  by  the  oxidation  of  tartaric  acid,  and  had  also 
converted  alcohol  into  acetic  acid  by  the  aid  of  platinum  black.  In 
1826  Hennel  had  synthesized  alcohol  from  olefiant  gas.1  Again,  in 
1828,  Wohler  found  that  in  attempting  to  obtain  ammonium  cyanate 
by  the  action  of  ammonium  chloride  upon  silver  cyanate,  or  ammonia 
on  lead  cyanate,  a  crystalline  compound  was  formed  which  was  iden- 
tified as  urea,  a  substance  only  previously  found  in  urine.  But  none 
of  these  artificially  prepared  substances  was  entirely  independent  of 
an  animal  or  vegetable  origin.  Even  the  cyanates  were  derived  in 
the  first  instance  from  potassium  ferrocyanide,  in  the  preparation 
of  which  animal  matter  was  employed.  These  facts  did  little  to 
disturb  the  belief  in  a  vital  force.  Both  Dobereiner's  and  Wohler's 
discoveries  are  referred  to  by  Berzelius  in  his  Jaliresbericht*  but  it  is 
clear  that  the  rare  example  of  isomerism  furnished  by  the  conver- 
sion of  ammonium  cyanate  into  urea  created  a  far  deeper  impression 
than  the  realization  of  this  much  quoted  synthesis. 

Before  the  year  1832  the  only  organic  substance  from  which  a 
number  of  simple  derivatives  had  been  obtained  was  alcohol.  With 
sulphuric  acid  it  was  known  to  yield,  according  to  the  conditions  of 
the  experiment,  sulphovinic  acid,  ether,  olefiant  gas  and  a  substance 
known  as  oil  of  wine  of  the  formula  (CH2)n  ;  with  hydrochloric  acid 
it  gave  hydrochloric  ether;  with  nitric  acid,  nitric  (nitrous)  ether;  with 
acetic  acid,  acetic  ether,  and  with  oxalic  acid,  oxalic  ether.  Further,  the 
oil  of  the  Dutch  chemists,  as  it  was  called,  was  obtained  by  combining 
olefiant  gas  with  chlorine,  and  Hennel  showed  that  sulphovinic  acid 
was  formed  by  the  union  of  olefiant  gas  and  sulphuric  acid.3  The 
relationship  of  alcohol  to  its  derivatives  was  a  matter  of  general 

1  Phil  Trans.,  1826,  240;  1828,  365;  Pogg.,  Ann.,  1827,  0,.21  ;  1828,  14,  282. 
See  also  Chemical  Synthesis  of  Vital  Products,  p.  2,  by  K.  Meldola,  1905. 
3  Jahresb.,  1823,  2,  160;  1829,  9,  266. 
8  Pogg.,  Ann.,  1828,  14,  273 ;  Phil.  Trans.,  1826,  Pt.'2,  240. 


10 


OEGANIC  CHEMISTRY 


speculation  which  had  free  play,  since  no  recognized  method  for 
ascertaining  molecular  weights  existed. 

The  Etherin  Theory.  In  1828  Dumas  and  Boullay l  propounded 
a  theory  which  was  intended  to  show  the  relationship  of  these 
substances.  It  was  based  upon  an  observation  of  Gay-Lussac's  that 
the  vapour  density  of  ether  was  equivalent  to  that  of  one  volume  of 
olefiant  gas  and  half  a  volume  of  water  vapour,  whereas  that  of 
alcohol  was  equivalent  to  half  a  volume  of  olefiant  gas  and  half 
a  volume  of  water  vapour.  Dumas  and  Boullay  regarded  alcohol, 
ether,  and  all  their  derivatives  as  containing  one  common  group  of 
elements,  olefiant  gas,  which  had  the  formula  2C2H2,  corresponding 
to  the  modern  C2H4  (the  atomic  weight  of  carbon  was  derived  by 
Dumas  from  the  vapour  density  of  marsh  gas  and  olefiant  gas,  which 
he  wrote  CH2  and  C2H2  respectively,  giving  the  number  6  to  carbon). 
To  the  central  group  Berzelius  gave  the  name  of  etherin,  by  which  he 
signified  oil  of  wine  and  denoted  it  by  the  formula 2  C4H8 ,  but  the 
fundamental  idea  was  the  same  in  both,  and  the  theory  was  hence- 
forth known  as  the  etherin  theory. 

In  addition  to  presenting  a  series  of  related  compounds  as  contain- 
ing a  common  group  or  radical,  it  explained  Kennel's  preparation  of 
sulphovinic  acid  from  ethylene  and  sulphuric  acid,  the  existence  of 
oxanie thane  (oxamic  ester)  obtained  by  Dumas  from  oxalic  ester  and 
ammonia  gas  and  the  curious  inflammable  platinum  organic  com- 
pounds of  Zeise,  which  the  latter  prepared  by  the  action  of  alcohol  on 
platinic  chloride  and  which  contained  no  oxygen.8 

An  essential  part  of  Dumas  and  Boullay's  theory  was  to  institute 
a  comparison  between  etherin  and  its  derivatives  and  ammonia  and 
its  compounds,  which  were  written  as  follows : 


Olefiant  gas 
Hydrochloric 

ether 
Ether 
Alcohol 
Acetic  ether 
Nitric  ether 
Oxalic  ether 
Oxamethane 
Sulphovinic 

acid 

Zeise's  com- 
pound 


Formulae  of  Dumas 

and  Boullay. 
2C2H2 

2C2H2+HC1 

4C2H2  +  H20 
4C2H2  +  2H20 


Formulae  of 
Berzelius. 
C4H8 

Ammonia  and  its 
Compounds. 
N2H6 

C4H8+2HC1 

N2H6+2HC1 

C4H8+H20 
C4H8  +  2H20 

W^o 

4C2H2 + N2O5  +  H20 
4C2H2  +  C4O3  +  H20 
4C2H2+C403+NH3 

4C2H2+2S03  +  2H2C 
4C2H2+2PtCl2 


C4H8+Pt2Cl4 


1  Ann.  Chim.  Phys.,  1828,  (2),  36,  294 ;  (2),  37,  15. 
9  Jahresb.,  1832,  12,  303.  3  Annalen,  1834,  0,  1. 


THE   ETHERIN  THEORY  11 

Dumas  and  Boullay  went  so  far  as  to  state  that  olefiant  gas,  were 
it  but  soluble  in  water,  would  exhibit  alkaline  properties,  and  they 
even  attempted  to  extend  their  theory  so  as  to  embrace  compounds  like 
the  fats  and  oils,  which  were  assumed  to  possess  an  imaginary  hydro- 
carbon radical  united  to  ether,  and  even  the  sugars  which  were 
described  as  carbonates  of  etherin.  The  theory  found  many  supporters 
and  long  held  its  ground  in  France.  Berzelius,  on  the  other  hand, 
gave  it  a  half-hearted  reception,1  which  soon  changed  to  undisguised 
hostility.  He  pointed  out  that  the  existence  of  the  radical  C4H8 
might  be  accepted  as  a  mere  matter  of  convenience,  but  that  the 
formula  for  alcohol  could  be  equally  well  represented  by  either 
C4HS  +  2H.O  or  C4H10O  +  H/).  The  fact  of  alcohol  yielding  olefiant 
gas  was  no  more  a  reason  for  the  presence  of  this  group  in  alcohol 
than  there  was  for  the  pre-existence  of  nitrous  oxide  in  nitrate  of 
ammonia  merely  because  nitrous  oxide  was  evolved  on  heating. 
If  olefiant  gas  were  alkaline,  then  surely  alcohol  and  ether,  which 
were  soluble  hydrates,  should  also  have  alkaline  properties.  More- 
over, though  olefiant  gas  could  be  prepared  from  alcohol,  neither 
alcohol  nor  ether  could  be  formed  by  the  reverse  process  of  adding 
water  to  olefiant  gas,  and  the  analogy  with  ammonia  broke  down. 

Furnished  with  fresh  weapons  Berzelius  returned  to  the  attack  in 
the  following  year.*  Liebig  and  Wohler  had  shown  that  sulphovinic 
acid  had  the  formula  C4H8  +  2SO3  +  2H20,  containing,  therefore,  two 
atoms  (molecules)  of  basic  water,  yet  it  only  saturated  one  atom  of 
base,  and  consequently  the  remaining  atom  of  water  must  be  an 
integral  part  of  the  organic  constituent,  just  as  it  was  of  ammonia  in 
the  sulphate  N2H8O  +  SO3. 

Growth  of  the  Radical  Theory.  We  can  now  realize  how  matters 
stood  when  Liebig  and  Wohler,  in  the  memoir  to  which  reference  has 
been  made,  brought  the  first  unassailable  evidence  of  the  existence 
of  an  organic  compound  radical.  A  series  of  substances  had  been 
obtained  which  were  readily  convertible  into  one  another  by  simple 
reactions  such  as  chemists  were  familiar  with  in  inorganic  chemistry. 
They  contained  one  common  group  of  elements  C14H10O2  to  which  the 
name  lenzoyl  (benz,  the  root  of  benzoic,  and  vAi?,  substance)  was  given. 
The  compounds  were  written  as  follows : 

C14H10O2  +  H2  Benzoyl  hydride  (bitter  almond  oil) 

C14H10O2  +  0  +  H2O        Benzoic  acid 

CuH1002  -I-  C12  Benzoyl  chloride 

1  Jahresb.,  1828,  8,  292.  *Jahresb.,  1833,  13,  192. 


12  ORGANIC  CHEMISTRY 

CUH10O2  +  Br2  Benzoyl  bromide 

CUH1002  + 12  Benzoyl  iodide 

CUH10O2  +  N2H4  Benzamide 

CUH10O2  +  C2N2  Benzoyl  cyanide 

CUH10O2  +  S  Benzoyl  sulphide 

CUH10O2  +  O  +  C4H100  Benzoic  ether 

This  was  not,  however,  the  first  example  of  a  compound  radical. 
In  1815  Gay-Lussac,  in  controlling  Bertholet's  experiments  on  the 
composition  of  hydrocyanic  acid,  obtained  cyanogen  by  heating 
mercuric  cyanide,  and  by  the  action  of  the  halogens  on  hydrocyanic 
acid  prepared  the  chloride,  bromide,  and  iodide  of  cyanogen.  This 
example  of  a  compound  radical,  as  well  as  that  of  sulphocyanogen 
and  ammonium,  were  overlooked,  partly  because  they  were  ranked 
with  inorganic  substances,  partly  because  Lavoisier's  original  con- 
ception of  a  radical  necessarily  implied  that  part  of  a  substance  of 
which  the  other  part  was  oxygen.  It  should  be  observed  that  in 
benzoyl  we  have  a  modification  of  Lavoisier's  definition  of  a  compound 
radical  inasmuch  as  benzoyl  contained  oxygen. 

Liebig  and  Wohler's  discovery  was  soon  followed  by  that  of  other 
radicals.  The  radicals  of  salicylic  and  cinnamic  acids  were  shown, 
the  former  by  Piria,  and  the  latter  by  Dumas  and  Peligot,  to  form 
each  a  series  of  derivatives  similar  to  that  of  benzoic  acid,  and  were 
termed  respectively  salicyl  and  cinnamyl.  Ten  years  later  the  theory 
of  the  compound  radical  received  further  confirmation  in  a  brilliant 
research  of  Bunsen  upon  cacodyl. 

In  1760  Cadet  obtained  by  the  distillation  of  potassium  acetate 
with  oxide  of  arsenic  a  fuming  and  fetid  liquid,  which  inflamed 
spontaneously  in  the  air  and  was  extremely  poisonous.  It  was  called 
'  Cadet's  fuming  liquid '.  These  uninviting  properties  deterred 
chemists  for  seventy  years  from  satisfying  any  curiosity  they  might 
have  conceived  as  to  its  composition,  and  they  contented  themselves 
with  stating  its  properties  and  method  of  preparation. 

Dumas  was  the  first  to  analyse  it,  and  gave  it  the  formula  C8H12As2; 
but  Bunsen  soon  afterwards  ascertained  that  the  liquid  prepared  by 
the  above  method  contained  oxygen  and  had  the  formula  C4H12As20, 
which  he  called  cacodyl  oxide  (ramoSi??,  stinking).1  From  this  he 
obtained,  by  means  of  the  halogen  acids,  cacodyl  chloride,  bromide, 
iodide,  and  also  the  cyanide,  fluoride,  sulphide,  selenide,  cacodylic 
acid,  and,  finally,  by  the  action  of  metallic  zinc  on  the  chloride,  the 


1  Pogg.,  Ann.,  1837,  40,  219  ;  1837,  42,  145  ;  Annalen,  1841,  37,  1 ;  1842,  42,  14 ; 
1843,  46,  1  ;  Oswald's  Klassiker,  No.  27. 


GROWTH  OF  THE   RADICAL  THEORY  13 

radical   cacodyl  itself  C4H12As2,  which    he    also   named    akarsin 
(alcohol-arsenic)  to  indicate  its  relation  to  alcohol. 

C4H12O2     Alcohol 

C4H12As2  Alcarsin 

He  termed  cacodyl  a  true  organic  element  possessing  the  character 
of  a  metal.  This  analogy  is  readily  understood  if  we  write  Kd  for 
the  cacodyl  radical  and  compare  it  with  a  metal  such  as  calcium. 

Cacodyl  C4H12As2  Kd  Ca 

Cacodyl  oxide  CJIlzAszO  KdO  CaO 

Cacodyl  chloride          C4H12As2Cla        KdCl3          CaCl, 
Cacodyl  cyanide  C4H12As2Cy2        KdCy2         CaCy, 

Cacodyl  sulphide         C4H18AsaS  KdS  CaS 

^- 

Liebig's  Definition  of  a  Compound  Radical.  Although  this 
research  was  the  product  of  a  later  period,  Liebig's  original  definition 
of  a  compound  radical  has  undergone  no  change.1  He  says,  speaking 
of  cyanogen,  '  we  call  this  a  radical  because  (1)  it  is  the  invariable 
constituent  of  a  series  of  compounds,  (2)  it  can  be  replaced  by  other 
simple  bodies,  and  (3)  in  its  combinations  with  a  simple  body  the 
latter  may  be  substituted  by  equivalents  of  other  simple  bodies.  Of 
these  three  conditions,  two  must  be  fulfilled.'  These  conditions 
made  it  essential  that  in  a  series  of  simple  reactions  the  radical  or 
group  of  elements  should  be  shown  to  remain  intact,  and  not  only  to 
be  capable  of  combining  with  elements  to  form  compounds,  but  also 
of  being  replaced  by  them. 

It  is  evident  from  this  statement  that  the  author  conceived  the 
elements  of  which  the  radical  was  composed  to  be  united  by  a  bond 
which  joined  them  together  more  firmly  than  the  other  elements  in 
the  compound.  The  particular  group  composing  the  radical  upon 
which  the  choice  fell  was  a  matter  of  much  diversity  of  opinion.  This 
is  specially  noteworthy  in  the  case  of  ether  and  alcohol  and  their 
derivatives. 

The  Radical  '  Ethyl ' .  We  have  already  referred  to  the  etherin 
theory  of  Dumas  and  Boullay  and  the  comparison  which  they  drew 
between  olefiant  gas  and  ammonia.  There  existed  at  the  time 
another  view  of  the  constitution  of  ammonia  and  its  salts.  The 
theory  that  ammonium  played  the  part  of  a  metallic  radical  in  its 
salts  was  suggested  by  Davy,  and  afterwards  supported  by  Ampere 
and  Berzelius.  It  appealed  to  the  dualists,  for  it  enabled  them  to 
establish  an  analogy  between  the  composition  of  the  salts  of  ammonia 

1  Annalm,  1838,  25,  2. 


14  OKGANIC  CHEMISTRY 

and  those  of  the  alkali  metals.  This  view  was  now  revived  by 
Liebig,  and,  in  place  of  etherin  C4H8  and  its  analogue  ammonia  NH3, 
the  new  radical  C4H10,  termed  by  Liebig  etheryl  or  ethyl1  (alOrjp, 
ether,  and  v\rj,  substance),  took  its  place  beside  ammonium. 

C4H10C12  Hydrochloric  ether.        N8H8C12  Ammonium  chloride. 

C4H100  Ether.  N2H80  Ammonium  oxide 

(present  in  the  salts). 

C4H100  +  H2O        Alcohol.  N2H80-fH20       Ammonium  hydrate. 

C4H100+N205        Nitric  ether.  N2H80-fN205      Ammonium  nitrate. 

C4H100  +  C4H603   Acetic  ether.  N2H80  +  C4H603  Ammonium  acetate. 

Berzelius  who  had,  as  we  have  seen,  abandoned  the  etherin 
theory,  accepted  the  new  doctrine,  for  its  basis  was  dualistic,  inas- 
much as  ether  appeared  as  an  oxide.  He  and  Liebig,  however, 
held  different  views  on  the  constitution  of  alcohol.  Liebig  regarded 
it,  from  its  relation  to  ether,  as  the  hydrate  of  ether,  whereas 
Berzelius  considered  it  to  be  the  oxide  of  a  different  radical,  C^H6.2 
One  reason  advanced  by  Berzelius  was  the  difference  in  properties 
between  sulphovinic  acid  obtained  by  the  action  of  sulphuric  acid 
on  alcohol,  and  isethionic  acid,  prepared  by  Magnus  by  the  action 
of  sulphuric  acid  (S03)  on  alcohol  and  ether.3 

The  two  substances  are  isomeric  and  saturate  the  same  amount  of 
base,  but  the  barium  salt  of  sulphovinic  acid  contains  an  atom  more 
water  than  that  of  isethionic  acid,  and  they  are  in  other  respects 
totally  distinct  substances.  '  It  is  clear,  therefore/  writes  Berzelius 
in  the  JaJireslericht  for  1833,  'that  this  atom  of  water  cannot  be 
present  as  water  of  crystallization,  but  must  be  there  in  another 
form,  and  this  other  form  can  be  nothing  else  than  a  form  of  ether. 
It  naturally  follows  that  alcohol  and  ether  are  not  hydrates  of  the 
same  base,  although  they  may  be  so  regarded.' 

The  two  formulae  of  the  barium  salts  would  therefore  appear  as 
2C2H6O  +  2S03  +  BaO  for  the  sulphovinate,  and  C4H100  +  2S03  +  BaO 
for  the  isethionate.4 

1  Annalen,  3834,  9,  1.  3  Jahresb.,  1833,  13,  194. 

8  Annalen,  1833,  6,  163;  Pogg.,  Ann.,  1833,  27,  367. 

*  According  to  modern  views  the  formation  of  isethionic  acid  from  ethionic 
acid  and  carbyl  sulphate  would  be  represented  as  follows  :  alcohol  and  sulphur 
trioxide  unite  to  form  carbyl  sulphate. 


CH2    .   S02 
Carbyl  sulphate. 

Carbyl  sulphate  is  decomposed  by  water,  first  into  ethionic,  and  finally  into 
isethionic  acid  : 

CH2.O.S03H  CH2.OH 

CH2.S03H  CH2.S03H 

Ethionic  acid.  Isethionic  acid. 


THE  RADICAL   ' ETHYL'  15 

But  there  were  additional  reasons.  Berzelius  contended  that  the 
dissimilarity  in  properties  of  alcohol  and  ether  could  not  be  attributed 
to  the  presence  or  absence  of  water.  Nor  was  it  probable  that  in 
alcohol  the  water  could  have  so  strong  an  affinity  for  the  ether  (with 
which  in  the  free  state  it  cannot  be  induced  to  combine)  that  a 
dehydrating  agent,  like  barium  oxide,  can  produce  from  alcohol  no 
trace  of  ether. 

Growth  of  Organic  Chemistry,  1830-1840.  Whilst  the 
various  disputants  were  urging  the  claims  of  rival  radicals,  their 
activity  in  the  laboratory  was  not  suspended.  Organic  chemistry 
was  steadily  advancing  and  widening  its  boundaries  by  new  dis- 
coveries, which  followed  one  another  in  rapid  succession.  The 
foundation  of  the  great  edifice  of  aromatic  chemistry  was  being  laid, 
upon  which  the  next  generation  was  to  build  new  and  important 
industries.  Mitscherlich  had  obtained  benzene  from  benzoic  acid 
by  distillation  with  lime,  identical  with  Faraday's  hydrocarbon 
from  oil  gas,  and  formed  nitrobenzene,  benzenesulphonic  acid, 
clilorobenzene  and  certain  other  derivatives.  Runge  had  found 
tyanol,  afterwards  identified  as  aniline,  and  carbolic  acid  in  coal-tar. 
Liebig  had  obtained  chloral  and  chloroform  by  the  action  of  chlorine 
on  alcohol,  and  had  determined  the  composition  of  acetone,  alde- 
hyde, and  acetal.  Dumas  and  Peligot  had  isolated  methyl  alcohol  in 
the  pure  state  from  wood  spirit,  and  Dumas  and  Cahours  had 
prepared  amyl  alcohol  from  fusel  oil.  In  both  cases  a  number  of 
derivatives  had  been  obtained  offering  a  close  analogy  with  those 
from  ordinary  alcohol.  Zeise  had  discovered  the  mercaptans,  and 
Regnault  had  studied  the  action  of  potash  on  Dutch  liquid,  and 
obtained  the  compound  we  now  call  vinyl  chloride.  The  formula 
of  the  new  compound  was  written  C4H6C12  and,  according  to  Regnault, 
contained  the  radical  C4H6 ,  \vhich  he  termed  aldehydene,  subsequently 
changed  to  acetyl.  In  the  meantime  a  partial  reconciliation  had 
been  arrived  at  between  Liebig  and  Dumas,  when  the  latter  was  won 
over  to  the  '  radical '  views  of  Liebig,  and  the  result  was  a  joint  article 
which  appeared  in  1837,  and  of  which  the  following  is  an  abstract.1 

'  Organic  chemistry  possesses  its  own  elements,  which  sometimes 
play  the  part  of  chlorine  or  oxygen  (e.  g.  cyanogen),  and  sometimes 
that  of  a  metal  (e.  g.  ethyl,  benzoyl,  cacodyl).  Cyanogen,  amide, 
benzoyl,  the  radicals  of  ammonia,  of  the  fats,  of  alcohol  and  its 
derivatives,  are  the  true  elements  of  organic  nature,  whereas  the 

1  /.  prakt.  Chem.,  1837,  U,  298;  Compt.  rend.,  1837,  5,  567. 


16  ORGANIC  CHEMISTRY 

simplest  constituents,  carbon,  hydrogen,  oxygen,  and  nitrogen,  only 
reappear  when  the  organic  matter  is  completely  destroyed.' 

The  truce  did  not  last  long,  and  when  the  new  radical,  acetyl, 
appeared,  Liebig  seized  upon  it  in  order  to  explain  the  constitution  of 
those  compounds,  which,  like  Zeise's  platinum  compounds  and 
Dumas'  oxamethane,  contained  no  ethyl  radical,  without  having 
recourse  to  the  etherin  theory  to  which  he  was  a  firm  opponent. 
Like  his  predecessors  he  established  an  analogy  with  ammonia  and 
its  derivatives  by  introducing  into  the  latter  the  radical  amide.1 

Letting  Ac  stand  for  acetyl,  C4H6,  and  Ad  for  amide,  N2H4,  the 
series  of  compounds  appeared  with  the  following  formulae : 

AcH3  Olefiant  gas.  AdH2  Ammonia. 

AcH4  Ethyl.  AdH4  Ammonium. 

AcH40  Ether.  AdH40  Ammonium  oxide. 

AcH4Cl2  Ethyl  chloride.  AdH4Cla  Salammoniac. 

AcH40+H20  Alcohol. 

AcH4S-fH2S  Mercaptan.  AdH4S-fH2S  Ammonium  sulphide. 

AcH2  +  2S033  Isethionic  acid.  AdH2  +  S03  Rose's  anhydrous 

ammonium  sulphate. 

2Ad+2CO  Urea. 

Ad  +  2CO  Oxamide. 
AcH4,  Ad  +  2C203    Oxamethane. 

The  new  theory  also  enabled  Liebig  to  include  in  his  scheme 
aldehyde,  chloral,  and  acetic  acid,  which  appeared  as  follows : 

C4H6,0  +  H20    Aldehyde 
C4C16,0  +  H20    Chloral 
C4H6,O3  +  H^O  Acetic  acid 

The  introduction  of  the  new  acetyl  radical  C4H6  into  alcohol  and 
its  derivatives  never  actually  replaced  the  older  ethyl  radical  which 
continued  to  be  used  by  the  German  chemists,  whilst  etherin  was 
retained  in  France. 

The  Chemistry  of  Compound  Radicals.  With  the  year  1840 
the  first  chapter  in  the  history  of  organic  chemistry  may  be  said  to 
close.  Although  organic  chemistry  was  still  concerned  with  products 
of  a  vital  force,  and  with  the  compounds  derived  from  them  by  the 
action  of  chemical  reagents,  the  dominant  idea  was  the  compound 
radical.  It  was  around  the  compound  radicals  that  the  various  organic 
substances  were  grouped.  In  Liebig's  treatise,  which  was  published 

1  Annalen,  1839,  30,  129. 

a  This  formula  represents  the  anhydride  of  the  acid.  After  Regnault's  dis- 
covery of  its  preparation  from  sulphur  trioxide  and  olefiant  gas,  it  was  usually 
represented  as  a  compound  of  etherin  and  sulphuric  anhydride 


THE  CHEMISTRY  OF  COMPOUND  RADICALS        17 

in  1840,  all  the  well-defined  compound  radicals,  whether  containing 
carbon  or  not,  are  included.  Separate  chapters  are  devoted  to  amide, 
oxide  of  carbon  (the  radical  of  oxalic  acid),  cyanogen,  benzoyl,  cinn- 
amyl,  salicyl,  ethyl,  acetyl,  methyl,  formyl,  cetyl,  amyl,  and  glyceryl. 
They  were  hypothetical  groups  which  might  or  might  not  be 
capable  of  separation,  but  their  admission  was  a  necessity  and  their 
existence  in  the  compound  more  than  probable.  Organic  chemistry 
was  defined  by  Liebig  as  the  chemistry  of  the  compound  radical. 

Theory  of  Substitution.  Meanwhile  a  movement  had  begun, 
which,  gathering  force  as  it  advanced,  swept  away  two  ruling 
principles,  the  one,  the  electro-chemical  theory,  the  other,  the  pre- 
existence,  as  it  was  termed,  of  radicals  as  unalterable  groups  of 
elements,  or  proximate  constituents  of  organic  compounds.  It 
was  the  direct  result  of  the  study  of  a  chemical  process  which 
has  been  termed  substitution.  The  idea  of  substitution  was  not 
a  new  one.  The  substitution  of  a  metallic  oxide  for  water  in  an 
acid  hydrate  to  form  a  salt,  and  Mitscherlich's  discovery  that 
the  crystalline  form  of  a  compound  is  often  retained  when  one 
element  replaces  another,  were  well  known  to  chemists.  Among 
organic  compounds,  the  action  of  chlorine  on  hydrocyanic  acid  had 
been  found  by  Gay-Lussac  to  give  cyanogen  chloride,  Liebig  and 
Wohler  had  obtained  benzoyl  chloride  from  bitter  almond  oil,  and 
Faraday  prepared  carbon  sesquichloride,  C2C16,  from  Dutch  liquid 
in  the  same  manner. 

Dumas'  Law  of  Substitutions.  In  1834  Dumas'  attention  had 
been  directed  to  the  action  of  chlorine  on  organic  compounds  by 
observing,  as  Gay-Lussac  had  previously  done,  that  when  wax  is 
bleached  by  chlorine  a  portion  of  the  hydrogen  is  replaced  by 
chlorine.  He  found  also  that,  when  chlorine  acts  upon  turpentine, 
for  every  volume  of  hydrogen  removed  an  equal  volume  of  chlorine 
enters.  He  then  repeated  Liebig's  experiments  on  the  action  of 
chlorine  and  bleaching  powder  upon  alcohol,  and  carefully  analysed 
the  products.  From  the  result  of  these  researches  he  formulated,  in 
1834,  the  following  empiric  law  of  substitutions.1 

1.  If  a  body   containing  hydrogen  be  acted  upon   by  chlorine, 
bromine,  or  iodine,  or  oxygen,  for  every  atom  of  hydrogen  which 
it  loses,  it  takes  up  one  atom  of  chlorine,  bromine,  or  iodine,  or  half 
an  atom  of  oxygen. 

2.  If  the  compound,  besides  hydrogen,  contains  oxygen,  the  same 
rule  holds  without  modification. 

1  Ann.  Chim.  Phys.,  1834,  56,  113. 
FT.  I  O 


18  ORGANIC  CHEMISTRY 

3.  If  a  body  contains  water  in  addition  it  first  loses  the  hydrogen 
of  the  water  without  replacement ;  if  hydrogen  is  then  removed,  it 
is  replaced  in  the  above  manner. 

The  first  two  propositions  require  no  comment ;  the  third  was 
introduced  in  order  to  explain  such  reactions  as  the  conversion  of 
alcohol  into  chloral,  and  alcohol  into  acetic  acid.  The  reactions 
were  written  thus: 

(C8H8  +  H402)  +  4C1  =  C8H802  +  4HC1 

Alcohol.  Aldehyde. 

C8H8O2  +  12C1  =  C8H2C1602  +  6HC1 
Chloral. 

(C8H8  +  H402)  +  04  =  (C8H402  +  H402)  +  H402 

Alcohol.  Acetic  acid. 

The  study  of  substitution,  to  which  Dumas  gave  the  name  of 
metalepsy  (i*era\i$tst  exchange),  attracted  many  of  the  French 
chemists,  among  whom  were  Peligot,  Malaguti,  and  Regnault,  who 
studied  the  action  of  chlorine  on  ethyl  chloride  and  ether,  and 
Laurent,  who  investigated  its  action  on  naphthalene,1  and  with 
Regnault,  on  Dutch  liquid.  As  a  result  of  Laurent's  observations, 
the  following  rules  were  added  to  the  laws  of  Dumas : 

'  When  chlorine,  bromine,  oxygen,  or  nitric  acid  replace  hydrogen 
in  a  hydrocarbon,  the  hydrochloric  acid,  hydrobrornic  acid,  nitrous 
acid  or  water  formed  are  either  liberated  or  remain  combined  with 
the  product J.2 

Laurent's  Nucleus  Theory.  Upon  this  foundation  Laurent 
constructed,  in  1837,  his  nucleus  theory.3  Laurent  assumed  that 
every  organic  compound  contained  a  hydrocarbon  nucleus  or  radical. 
These  were  the  primary  nuclei  (noyaux  fondamentaux),  and  were  so 
chosen  that  the  elements  composing  them  were  present  in  even 
numbers  (see  p.  28).  Other  elements  or  groups  of  elements  can  be 
added  on  to  the  primary  nuclei.  When  the  hydrogen  in  the  primary 
nucleus  was  replaced  by  equivalents  of  other  elements,  the  halogens, 
oxygen,  nitrogen,  &c.,  secondary  nuclei  (noyaux  derives)  were  pro- 
duced, and  the  compound  remained  intact.  It  was  only  when  the 
elements  of  the  nucleus  were  permanently  removed  that  complete 
decomposition  of  the  substance  ensued.  The  primary  nucleus  was 
compared  to  a  prism,  the  solid  angles  of  which  corresponded  to 
carbon,  and  the  edges  to  hydrogen.  If  these  edges  are  replaced  by 
others  the  geometrical  form  is  unchanged,  but  should  they  be 

1  Ann.  Chim.  Phys.,  1835,  59,  196.  a  Ann.  Chim.  Phys.,  1836,  60,  223. 

3  Ann.  Chim.  Phys.,  1837,  61,  125;  see  also  Gmelin's  Handbook,  7,  18,  30. 


LAURENT'S  NUCLEUS  THEORY         19 

removed,  the  system  falls  to  pieces.  To  the  central  prism  other 
geometrical  figures  can  be  attached,  on  removing  which  the  original 
form  reappears.  The  following  examples  may  serve  to  illustrate  the 
theory.  By  the  alternate  action  of  chlorine  and  potash  on  olefiant 
gas,  a  number  of  chlorinated  compounds  had  been  obtained.  These 
were  supposed  to  contain  the  primary  nucleus  C4H8.  The  compounds 
were  written  as  follows,  the  nomenclature  being  that  of  Dumas  and 
Peligot: 

Ether  ene  C4H8 

Etherene  hydrochlorate  (hydrochloric  ether)  C4H8  +  H2C12 

Chloretherase  (Regnault's  acetyl  chloride)  C4HGC12 

„  hydrochlorate  (Dutch  liquid)  C4HGC12  +  H2C12 

Chloretherese  C4H4C14 

„  hydrochlorate  C4H4C14  +  H2C12 

Chloretherise  C4H2C16 

,,  hydrochlorate  C4H2C16  +  H2Cla 

Chloretherose  C4C18 
Chloride  etherosique  (Faraday's  sesquichloride 

of  carbon)  C4C18  +  C14 

A  similar  series  was  derived  from  methylene  and  naphthalene, 
whilst  alcohol  and  its  oxidation  products  appeared  as  follows  : 

Alcohol  C4H8  +  H402 

Aldehyde         C4HG0  +  H2O 
Acetic  acid       C4H60  +  O2 

Although  Laurent's  formulae  bore  a  certain  resemblance  to  those 
of  the  etherin  theory,  they  really  embodied  an  important  new  prin- 
ciple, namely,  that  when  chlorine  and  bromine  replace  their  equivalent 
of  hydrogen,  the  former  take  the  place  of  the  latter,  and  play  to  some 
extent  the  same  part  in  the  new  compound,  in  consequence  of  which 
the  compound  retains  a  certain  similarity  to  the  parent  substance. 

The  theory  amounted  to  a  revolution.  We  cannot  wonder  that  it 
should  have  served  as  a  direct  challenge  to  Berzelius  and  the  followers 
of  the  electro-chemical  school.  The  principle,  once  admitted,  that 
chlorine,  an  electro-negative  element,  could  take  the  place  of  hydrogen, 
an  electro-positive  element,  and  do  so  without  changing  the  typical 
properties  of  the  new  compound,  was  to  shake  the  very  foundation 
of  dualism  ;  for  we  must  remember  that  it  was  this  opposite  negative 
and  positive  character  which  served  to  link  the  atomic  units  in  a 
compound ;  it  was  this  dual  conception  which  saw  a  new  hydro- 
carbon radical  in  every  compound  in  which  hydrogen  was  replaced 
by  another  element. 

o  P, 


20  ORGANIC  CHEMISTRY 

Berzelius  was  not  slow  in  replying.  His  first  contemptuous  com- 
ment on  the  new  formulae  of  Laurent  appeared  in  his  JaliresbericM 
for  1837 :  '  I  consider  it  superfluous  to  enlarge  further  on  such 
a  theory.'  He  then  directed  his  attack  against  Dumas,  who  at  once 
repudiated  the  revolutionary  views  of  Laurent : l  i  To  represent  me 
as  saying  that  when  chlorine  replaces  hydrogen  it  plays  the  part  of 
the  hydrogen,  is  to  attribute  to  me  an  opinion  against  which 
I  strongly  protest,  as  it  is  opposed  to  everything  I  have  written  on 
this  subject.  The  substitution  theory  expresses  only  the  relation 
which  exists  between  the  hydrogen  which  disappears  and  the  chlorine 
which  takes  its  place/  and  further  on,  '  It  is  an  empiric  rule  which  is 
of  value  so  long  as  it  holds ;  if  any  one  has  given  it  an  extension 
which  was  not  in  my  mind,  I  am  not  responsible.'  When,  how- 
ever, Dumas  afterwards  (1839)  obtained  trichloracetic  acid  by  passing 
chlorine  into  acetic  acid,  and  found  that  the  new  compound  not  only 
retained  the  characteristic  acid  property  of  the  original  substance, 
saturating  the  same  amount  of  base  and  forming  salts  and  esters,  but 
yielded  chloroform  with  potash,  as  acetic  acid  yielded  marsh  gas,  the 
analogy  between  the  two  was  complete,  and  Dumas  henceforth 
participated  in  Laurent's  views. 

'  It  is  clear,'  wrote  Dumas,  'that  if  I  accept  this  doctrine,  which  is 
based  upon  facts,  I  cannot  attach  any  weight  to  an  electro-chemical 
theory  which  has  been  the  dominant  idea  upon  which  Berzelius  has 
sought  to  construct  a  universal  system.' 

'But  these  electro-chemical  ideas,  this  special  polarity  which  is 
assigned  to  the  atoms  of  simple  bodies,  do  they  rest  upon  such  clear 
facts  that  they  may  rank  as  articles  of  faith?  Or,  if  they  are 
considered  as  hypotheses,  have  they  the  property  of  adapting  them- 
selves to  the  facts  with  such  certainty  that  they  can  be  utilized  in 
chemical  investigations  ?  It  must  be  conceded  that  such  is  not  the 
case.' 

'  Isomorphism — a  theory  based  upon  facts — has  been  a  true  guide 
in  mineral  chemistry,  and,  as  is  well  known,  has  little  in  common 
with  electro-chemical  theories.' 

'  Now,  in  organic  chemistry,  the  theory  of  substitution  plays  the 
same  part  as  isomorphism  in  inorganic  chemistry,  and  indeed  it  may 
happen  that  future  experience  will  show  that  both  views  are  related 
and  spring  from  the  same  cause,  which  may  be  combined  in  a 
common  expression.' 

'  For  the  present,  from  the  conversion  of  acetic  into  chloracetic 
acid  and  from  that  of  aldehyde  into  chloral,  from  the  fact  that  the 
1  Compt.  rend.,  1838,  6,  699. 


LAURENT'S  NUCLEUS  THEORY  21 

whole  of  the  hydrogen  is  replaced  by  chlorine,  volume  for  volume, 
without  changing  their  original  nature  we  must  conclude : 

*  That  there  exist  in  organic  chemistry  certain  types  which  remain  as 
such  even  after  their  hydrogen  has  been  replaced  by  an  equal  volume  of 
chlorine,  bromine,  or  iodine.' 

1  That  is  to  say,  the  theory  of  substitution  rests  on  facts,  and  on 
the  most  striking  facts,  of  organic  chemistry.' 

Dumas'  Theory  of  Types.  Dumas*  Theory  of  Types  incorporated 
his  former  law  of  substitutions  and  Laurent's  propositions  under  a 
somewhat  modified  form.1 

The  new  theory  was  introduced  in  order  to  emphasize  the  differ- 
ence between  the  substituted  compound  and  the  parent  substance  in 
which  the  general  character  or  type  was  preserved,  as  in  the  case  of 
acetic  and  chloracetic  acid  or  aldehyde  and  choral,  on  the  one 
hand,  and,  on  the  other,  those  substitution  products  (more  especially 
where  oxygen  replaced  hydrogen)  which  were  not  related  by  simi- 
larity of  properties  as  exemplified  by  alcohol  and  acetic  acid  or  marsh 
gas  and  formic  acid.  The  former  belonged  to  the  same  chemical  type 
and  the  latter  to  a  mechanical  or  molecular  type. 

The  two  groups  may  be  illustrated  by  the  following  examples, 
using  Dumas'  notation : 

Chemical  type.  Mechanical  type. 

Acetic  acid  C4H2H604  Alcohol  C4HCH6O2 

Chloracetic  acid    C4H2C16O4  Acetic  acid     C4H6H204 

Aldehyde  C4H2H602  Marsh  gas       C2H2H6 

Chloral  C4H2C16O2  Formic  acid    C2H203 

Dumas  pointed  out  that  the  properties  of  a  compound  lay  in  the 
arrangement  of  its  atoms  and  not  in  their  nature.  He  wrote : 
'  Lavoisier's  compounds  were  a  combination  of  a  combustible  element 
with  a  combustion  supporting  element.  The  electro-chemical  theory 
saw  in  these  an  electro-negative  and  an  electro-positive  element,  which 
is  a  modification  of  the  same  thing.  This  dualism  is  unnecessary  to 
explain  the  constitution  of  chemical  compounds,  the  parts  of  which 
may  be  compared  to  those  of  a  planetary  system  which  are  held 
together  by  mutual  attraction.  They  may  be  more  or  less  numerous, 
simple  or  complex.  In  the  constitution  of  the  compound  they  play 
the  same  part  as  the  simple  elements,  Mai's  or  Venus,  in  our  planetary 
system,  the  atomic  group  Earth  with  its  moon,  or  Jupiter  with  its 
satellites.  If  in  such  a  system  one  part  is  replaced  by  another  of 
a  different  kind,  equilibrium  is  maintained,  and,  if  the  replaced  and 

1  Ann.  Chim.  Phys.,  1840,  (2),  73,  73. 


22  ORGANIC  CHEMISTRY 

replacing  elements  resemble  one  another,  the  new  compound  has 
similar  chemical  properties  to  the  original  one.  If,  however,  they 
differ  they  belong  to  a  mechanical  system,  and  the  chemical  similarity 
is  difficult  to  recognize.' 

There  was  a  tendency  to  carry  this  theory  of  substitution  too  far, 
and  when  Dumas  suggested  that  even  carbon  might  undergo  substi- 
tution l  the  idea  was  ridiculed  by  Liebig.2 

In  the  meantime  Liebig  had  himself  contributed  to  the  overthrow 
of  the  electro-chemical  theory. 

The  Constitution  of  Organic  Acids.  Liebig  published  in  1838 8 
a  paper  '  On  the  Constitution  of  Organic  Acids  '. 

The  organic  acids,  it  must  be  remembered,  were  the  only  class  of 
substances  which  had  representatives  of  a  strictly  analogous  character 
among  inorganic  compounds,  and  any  new  theories  respecting  the 
structure  of  the  latter  would  necessarily  include  organic  acids. 
Before  discussing  the  subject  of  Liebig's  paper,  it  may  be  well  to 
gain  some  idea  of  the  views  generally  held  in  regard  to  the  constitu- 
tion of  acids  and  salts.  In  inorganic  chemistry  salts  of  oxyacids 
were  assumed  to  be  compounds  of  non-metallic  oxides  (called  acids) 
with  metallic  oxides  or  bases.  What  we  now  term  acid  was  the 
hydrate,  the  water  being  sometimes  termed  basic  water,  which  indi- 
cated that  in  the  formation  of  salts  it  was  replaceable  by  a  base. 
The  same  principle  was  applied  to  organic  acids  and  salts,  C203 
standing  for  oxalic  acid  and  C4H603  for  acetic  acid,  as  already  pointed 
out  (p.  7).  The  molecular  weight  of  an  acid  was  derived  from  the 
neutral  salts,  which  were  assumed  to  contain  one  equivalent  of  base 
united  toi  one  of  acid.  Thus,  sulphuric  acid  and  the  sulphates  were 
written  S03  +  H20,  S03  +  KO,  S03  +  AgO,  S03  +  CaO,  &c.  An  acid 
salt  was  a  neutral  salt  combined  with  an  equivalent  of  hydrated 
acid  ;  a  basic  salt  was  a  neutral  salt  with  an  additional  equivalent  of 
base.  Bisulphate  of  potash,  as  it  was  then  called,  had  the  formula 
S03 .  H20  +  S03  .  KO.  The  molecular  weight  of  an  organic  acid,  like 
citric  acid,  was  determined  from  its  silver  or  lead  salt.  According  to 
BerzeliusC4H4O4  -f  AgO  was  the  silver  salt  of  citric  acid,  C4H404  +  H20 
was  the  acid  hydrate,  and  C4H404  stood  for  the  acid.4  The  varying 
basicity  of  acids  was  not  recognized. 

There  was  one  exception  to  the  above  rules.     In  ordinary  sodium 
phosphate  the  ratio  of  one  equivalent  of  base  to  one  of  acid  would 

1  J.  prakt  Chem.,  20,  281.  2  Annalen,  1840,  33,  308. 

8  Annalen,  1838,  26,  113;  Ostwald's  Klassiker,  No.  20. 

*  These  formulae  are  obviously  incorrect.    The  correct  formula  of  the  acid 
hydrate  determined  by  the  method  described  would  be  C4H404  +  H40,8. 


THE   CONSTITUTION   OF  ORGANIC  ACIDS  23 

give  the  formula  (leaving  out  water)  P02i  +  NaO,  and  this  was  there- 
fore altered  to  P205  +  2NaO.  The  additional  molecule  of  water, 
which  we  now  recognize  as  forming  a  part  of  the  compound,  was 
included  in  the  total  water  of  crystallization.  But  a  curious  anomaly 
was  discovered  by  Clark.  In  attempting  to  prepare  anhydrous  sodium 
phosphate  he  found  that  the  ordinary  crystalline  phosphate  loses 
water  on  heating,  but  forms  a  new  salt,  which  has  properties  entirely 
distinct  from  common  sodium  phosphate,  and  does  not  unite  at  once 
with  water  to  form  the  original  compound.1  The  explanation  was 
given  by  Graham.  He  showed  that  there  exists  in  phosphoric  acid 
three  molecules  of  water,  which  are  replaceable  by  one,  two,  or  three 
molecules  of  base  as  follows : 

P205  +  3H20  ;  P205  +  2H20  +  NaO ;  P2O5  +  H20  +  2NaO  ; 
P2O5  +  3NaO;  P2O5  +  3Ag0.2 

He  distinguished  between  the  three  molecules  of  combined  water 
and  the  water  of  crystallization.  When  the  water  of  crystallization 
is  expelled  no  change  in  chemical  properties  results ;  but  if  the 
temperature  is  raised  so  as  to  drive  off  the  combined  water,  then 
salts  of  new  acids  are  formed.  He  prepared  in  this  way  the  sodium 
salts  of  pyro-  and  meta-phosphoric  acids  and  the  acids  themselves  by 
heating  ordinary  phosphoric  acid.  Graham  proved  in  this  way  that, 
whereas  ordinary  phosphoric  acid  has  three  replaceable  atoms  of 
water  and  is  therefore  tribasic,  pyrophosphoric  acid  contains  two  and 
is  dibasic,  and  metaphosphoric  acid  only  one,  and  is  therefore  mono- 
basic. 

Liebig  carried  these  researches  into  the  field  of  organic  chemistry. 
He  found,  for  example,  that  citric  acid,  like  phosphoric  acid,  formed 
three  series  of  salts,  and  that  the  analysis  of  the  acid  dried  at  100° 
did  not  agree  with  the  formula  of  Berzelius,  but  must  be  represented 
by  C12H10On  +  3H20.  The  analogy  between  phosphoric  and  citric 
acid  could  be  carried  even  further,  for  citric  acid  on  heating  loses 
water  and  is  converted  into  pyrocitric  acid  (citraconic  acid),  which  is 
dibasic.  The  old  rule  for  determining  the  molecular  weight  of  an 
acid  as  the  quantity,  which  saturates  one  equivalent  of  base,  had  to 
be  relinquished,  and  it  now  became  necessary  to  fix  beforehand  the 
basicity  of  the  acid  before  the  weight  of  the  molecule  could  be  ascer- 
tained. Liebig's  rule  was  to  find,  in  the  first  instance,  whether  the 
acid  was  capable  of  uniting  with  more  than  one  kind  of  base.  Thus 
tartaric  acid  was  dibasic,  as  it  formed,  in  the  case  of  Rochelle  salt 

1  Phil.  Trans.,  1833,  2,  280. 

2  The  equivalent  notation  in  which  phosphorus  had  double  its  present  combin- 
ing weight  represented  phosphoric  acid  as  P05 . 


24  ORGANIC  CHEMISTEY 

and  tartar  emetic,  a  tartrate  of  potash  and  soda,  and  of  potash  and 
antimony  oxide.  Sulphuric  acid,  on  the  other  hand,  remained 
monobasic,  because  a  sulphate  with  two  bases  was  unknown.  The 
acid  sulphates  continued  to  be  written  as  a  double  molecule  of  acid 
und  neutral  salt. 

At  the  close  of  the  paper  Liebig  reviews  the  whole  question  of  the 
presence  of  water  in  acids.  He  saw  that  the  separation  of  water  by 
the  action  of  a  base  on  an  acid  is  an  insufficient  explanation,  for  the 
oxygen  of  the  water  may  be  conceived  as  coming  from  the  metallic 
oxide  just  as  well  as  existing  already  combined  in  the  acid  hydrate. 
Moreover,  in  the  case  of  organic  acids  the  presence  of  water  is  im- 
probable, since  the  anhydrous  acids  are  purely  fictitious  entities, 
having  never  been  isolated. 

Liebig  revived  the  theory  of  Davy  (1809)  and  Dulong  (1819)  in 
regarding  acids  as  compounds  of  hydrogen,1  and  he  pointed  out,  as 
they  had  done,  that  it  was  illogical  to  separate  the  halogen  acids, 
hydrocyanic  acid,  and  hydrogen  sulphide  from  the  oxyacids  by  an 
artificial  barrier.  He  further  contended  that  if,  for  example,  silver 
sulphocyanide  is  Cy2S-f  SAg,  the  silver,  being  already  present  as 
sulphide,  should  not  separate  in  this  form  when  hydrogen  sul- 
phide acts  upon  the  salt,  but  the  reverse  actually  happens ;  if,  then, 
silver  sulphocyanide  is  Cy2S2  +  Ag  and  the  sulphocyanic  acid  is 
Cy2S2  -f  H2,  then  cyanic  acid  must  be  Cy202  +  H2,  and  so  on  with  the 
other  acids. 

The  conception  of  acids  as  compounds  of  hydrogen  did  not  at  once 
replace  the  older  view,  but  by  affording  a  simple  and  legitimate 
interpretation  of  the  formation  of  salts  from"  acids  by  the  substitu- 
tion of  hydrogen  by  a  metal,  it  threw  doubt  on  the  validity  of  the 
electro-chemical  theory. 

Gerhardt  and  Laurent.  The  theory  of  polybasic  acids  was 
subsequently  modified  and  expanded  by  Charles  Gerhardt  and 
Auguste  Laurent,  two  chemists  whose  names  will  always  be  linked 
together  in  the  history  of  chemical  science.  They  were  essentially 
reformers,  and,  like  many  ardent  reformers,  they  relentlessly  threw 
over  time-honoured  formulas  and  rode  rough-shod  over  cherished 
traditions.  In  their  place  they  set  up  empiric  rules  of  classification 
and  artificial  systems  of  notation  and  nomenclature  which  were 

1  Davy  supported  his  view  on  the  ground  that  potassium  chlorate  parts  with 
its  oxygen  on  heating  and  forms  potassium  chloride,  and  concluded  that  this 
stronger  affinity  of  the  metal  for  the  acid  than  for  oxygen  must  also  obtain 
among  the  oxyacids.  Dulong  based  his  opinion  on  the  constitution  of  the 
oxalates,  which  he  regarded  as  carbon  dioxide  united  to  the  metal,  thus : 
2C02  +  Pb  and  oxalic  acid  2C02  +  H2 . 


GERHARDT  AND  LAURENT  25 

difficult  to  understand  or  assimilate.  They  thus  alienated  the  sym- 
pathy of  their  fellow  chemists,  who  treated  them  in  a  manner  now 
painful  to  contemplate.  Although  no  action  on  the  part  of  Gerhardt 
and  Laurent  justified  such  treatment,  yet  it  must  be  confessed  that 
had  they  adopted  a  less  uncompromising  attitude  towards  men  who 
were  their  seniors  in  years  and  reputation,  it  would  have  gone  far  to 
soften  the  asperities  of  a  situation  which  they  unfortunately  helped 
to  create.1 

The  Unitary  System.  Gerhardt  and  Laurent  clearly  saw  the 
confusion  into  which  the  electro-chemical  theory  had  plunged  organic 
chemistry,  and  they  set  themselves  resolutely  to  extricate  it  from  the 
network  of  vague  and  unprofitable  speculations  in  which  it  had 
become  involved.  In  Laurent's  preface  to  his  Chemical  Method*  he 
writes  :  '  The  confusion  which  reigns  in  the  ideas  is  even  greater  than 
that  which  obtains  in  the  facts ;  for  the  principles  upon  which  the 
majority  of  chemists  rely  for  the  explanation  and  co-ordination  of 
facts  are  so  vague,  so  uncertain,  that  not  only  do  two  chemists  explain 
the  same  phenomena  in  two  different  ways,  but  even  one  and  the 
same  person  abandons  an  explanation  he  gave  yesterday  for  a  new 
one  he  proposes  to-day,  and  which  he  will  abandon  to-morrow  for 
a  third.'  Gerhardt,  in  his  Precis  de  Chimie  Organique  (1844),  says 
much  the  same  thing :  '  When  a  chemist  at  the  present  time  observes 
a  reaction  or  analyses  a  new  substance  his  first  care  is  to  conceive 
a  little  theory  which  shall  explain  the  phenomena  according  to 
electro-chemical  principles,  and  it  is  customary  to  create  a  hypo- 
thetical radical  in  order  to  adapt  these  principles  to  the  new  com- 
pound'; and  again,  'Six  or  seven  formulae  have  been  suggested  for 
alcohol,  each  observer  trying  to  support  his  own  ;  but  after  all,  each 
of  these  formulae  is  but  the  expression  of  one  or  two  reactions.  Upon 
one  thing  only  are  we  agreed,  and  that  is  the  empiric  formula  for 
alcohol.'  They  laid  aside  the  electro-chemical  theory  and  the  doctrine 
of  the  compound  radical  as  fixed,  proximate  constituents.  Organic 
compounds  were  no  longer  binary  compounds,  nor  an  arrangement 
of  certain  fixed  groups  of  elements.  They  were,  as  Dumas  expressed 
it,  edifices  simples,  simple  structures,  in  which  one  or  more  elements 
might  be  replaced  by  others.  In  opposition  to  the  binary  or  dualistic 
principle  the  system  was  termed  unitary.  Reactions  were  expressed 
by  equations,  but  not  in  the  customary  fashion,  for  they  did  not,  by 
introducing  radicals,  formulate  any  preconceived  internal  structure  of 

1  Vie  de  Charles  Gerhardt,  by  Grimaux  and  Gerhardt,  Masson  &  Cle,  Paris,  1900. 

2  Chemical  Method,  by  A.  Laurent,  trans,  by  W.  Odling,  Cavendish  Society's 
Publications,  London,  1855. 


26  OKGANIC  CHEMISTRY 

the  substances  taking  part,  but  merely  indicated  the  interchange  of 
constituents.  The  interchange  was  ascribed  to  the  stability  of  such 
combinations  as  water,  hydrochloric  acid,  carbonic  acid,  and  ammonia, 
which,  though  they  might  be  eliminated  in  the  process,  did  not  there- 
fore pre-exist  in  any  of  the  reacting  substances.  The  new  compound 
was  formed  by  a  double  decomposition  accompanied  by  the  removal 
of  a  part  of  the  reagent,  in  combination  with  part  of  the  reacting 
substance,  and  the  residues  or  restants  then  united. 

Gerhardt's  Theory  of  Residues.  This  embodied  the  principle 
of  Gerhardt's  system  of  residues  and  copulated  compounds  which 
appeared  in  1839.1  The  fundamental  idea  was  that  of  substitution, 
for,  according  to  Gerhardt's  rule,  '  the  element  which  is  removed  is 
replaced  by  the  equivalent  of  another  element  or  by  the  residue  of 
the  reacting  substance.  ' 

Gerhardt  represented  the  action  of  nitric  acid  on  benzene  thus: 
residue  product  eliminated  residue 

OHN 


Benzene  Nitric  acid 

The  residue  HN02  replaced  the  atoms  of  hydrogen  in  benzene.  The 
action  of  ammonia  on  benzoyl  chloride  was  expressed  in  a  similar 
way  :  C7H5OC1  +  NH3  =  C7H50(NH2)  +  HC1. 

Chlorine  is  removed  from  benzoyl  chloride  and  hydrogen  from 
ammonia,  and  the  two  residues  unite  to  form  benzamide. 

Conjugated  Compounds.  The  introduction  of  the  term  copula  or 
conjunct  arose  in  the  following  way  :  the  action  of  nitric  acid  on 
benzene,  or  sulphuric  acid  on  alcohol  has  no  parallel  in  that  of  an 
acid  on  a  base  in  inorganic  chemistry,  except  that  water  is  removed. 
Nitrobenzene  is  not  a  salt,  for  the  acid  and  base  cannot  be  replaced 
by  other  acids  or  bases,  and  in  sulphovinic  acid  and  the  sulphonic 
acids  the  sulphuric  acid  can  no  longer  be  detected  by  ordinary 
reagents.  The  original  constituents  are  completely  masked  and  the 
residues  may  have  their  atoms  differently  arranged.  They  are,  as 
Dumas  expressed  it,  in  a  form  of  substitution.2  The  action  of  nitric 
acid  on  benzene  can  be  represented  as  a  substitution,  as  already 
pointed  out,  but  not  that  of  sulphuric  acid  on  a  hydrocarbon  or 
alcohol,  for  the  saturation  capacity  of  the  acid,  according  to  the 
formulae  then  in  use,  remains  unchanged.  Different  bases  may 

1  Ann.  Chim.  Phys.,  1839,  72,  180. 

a  This  form  of  substitution  bears  a  close  resemblance  to  non-ionisable  com- 
pounds. 


CONJUGATED   COMPOUNDS  27 

saturate  the  acid,  but  the  organic  constituent  remains  permanently 
attached.  This  indifferent  residue  which  was  attached  to  the  acid 
was  called  by  Gerhardt1  the  copula  and  gave  rise  to  the  term 
copulated  compounds  (sels  copules),  which,  however,  very  soon  lost 
its  original  meaning.  When  the  different  basicities  of  the  acids 
was  recognized  and  sulphuric  acid  became  in  Gerhardt's  system 
dibasic  then  the  term  copulated  compound  or  conjugated  compound, 
as  it  was  called  by  Dumas,  received  the  following  interpretation:2 
'The  basicity  or  saturation  capacity  of  a  conjugated  compound  is 
always  less  by  one  unit  than  the  sum  of  the  basicities  belonging  to 
the  two  original  substances.'  Thus  benzenesulphonic  acid,  obtained 
from  benzene  and  sulphuric  acid,  is  monobasic,  whilst  benzene- 
sulphobenzoic  acid,  which  is  formed  from  benzoic  acid  and  sulphuric 
acid,  making  a  total  of  three  units  of  basicity,  is  dibasic.  When  the 
majority  of  organic  compounds  with  acids  was  embraced  by  the  term 
conjugated,  this  rule  was  applied  to  determine  the  basicities  of  acids. 
It  was  taken  as  a  proof  that  nitric  acid  was  monobasic  because  it 
formed  a  neutral  compound  with  benzene. 

Formulae  of  Gerhardt  and  Laurent.  The  attempt  to  attach  to 
the  terms  atom,  molecule,  volume,  and  equivalent  a  definite  and 
logical  meaning  and  to  establish  a  rational  system  of  chemical 
formulae  was  one  of  the  most  important  services  rendered  by 
Gerhardt  and  Laurent  to  chemical  science.  It  has  already  been 
stated  that  the  different  opinions  which  existed  on  the  interpretation 
and  in  the  application  of  these  expressions,  was  such  that  many 
chemists  had  renounced  the  atomic  system  of  Berzelius  and  taken 
refuge  in  Gmelin's  equivalent  notation.  Their  troubles  were  not  at 
an  end  and  difficulties  still  pursued  them.  It  could  scarcely  be 
otherwise  so  long  as  the  molecule  remained  an  indefinite  quantity. 

Gerhardt3  introduced  a  new  principle.  Keviving  Avogadro's  law, 
though  in  a  somewhat  restricted  sense,  he  proposed  to  make  the 
equivalents,  by  which  he  implied  molecules,  of  all  volatile  compounds 
and  gases  correspond  to  equal  volumes.  For  this  reason  he  reinstated 
Berzelius'  old  formula  H2O  for  water,  seeing  that  it  was  composed 
of  two  volumes  of  hydrogen  and  one  of  oxygen.  From  the  density 
of  mercury  vapour,  mercuric  oxide  received  the  formula  Hg20  in 
place  of  HgO,  and  the  other  basic  oxides  were  referred  to  the  same 
general  type  M20.  The  result  was  that  the  atomic  weights  of  all 

1  Ann.  Chim.  Phys.,  1839,  72,  186;  Gmelin's  Handbook,  7,  213. 

a  Precis  de  Chimie  Organique,  I,  98  ;  Laurent's  Chemical  Method,  p.  21J. 

*  Precis  de  Chimie  Organique,  I,  52. 


28  ORGANIC  CHEMISTRY 

the  metals  were  halved,  whereby  only  the  alkali  metals  and  silver 
received  their  present  values. 

Law  of  Even  Numbers.  In  his  original  memoir  published  in 
1842  Gerhardt1  determined  the  molecular  weight  by  taking  the 
weight  of  four  volumes  of  vapour  (compared  with  one  of  hydrogen). 
Finding  that  by  so  doing  the  number  of  molecules  of  water  or 
carbonic  acid  removed  in  a  chemical  decomposition  was  always  even, 
he  proposed  to  double  the  molecular  weights  of  these  substances 
whereby  they  would  become  equivalent  to  ammonia  N2H6  and 
correspond  to  four  volumes.  The  decomposition  of  benzoic  acid  into 
benzene  or  of  lactic  acid  into  lactide  were  usually  represented  as 
follows : 

C14H1204  =  C12H12  +  2C02 

Benzoic  acid.    Benzene. 

CJH1206  =  CGH804  +  2H20 

Lactic  acid.      Lactide. 

It  naturally  followed  that  every  organic  compound  contained  an 
even  number  of  carbon  atoms,  which  suggested  to  Gerhardt  and 
Laurent  the  idea  embodied  in  their  empiric  '  law  of  even  numbers ', 
according  to  which  the  sum  of  the  carbon  and  oxygen  atoms  on  the 
one  hand  and  of  hydrogen,  the  halogens,  metal  and  nitrogen,  on  the 
other,  was  divisible  by  2. 

These  views  were  very  soon  modified.  In  the  Precis  de  Chimie 
Organique  already  referred  to,  in  place  of  four  volumes  the  two  volume 
basis  of  molecular  weights  is  adopted,  and  all  the  formulae  are  halved. 
Hydrochloric  acid,  ammonia  and  water  appear  as  HCI,  NH3  and 
H20,  ether  is  C4H10O  and  alcohol  C2H6O,  &c.  The  Law  of  Even 
Numbers  was  restricted  to  the  sum  of  the  hydrogen  halogens, 
nitrogen,  phosphorus  and  arsenic  atoms.  The  law  still  holds,  and 
depends  on  the  quadrivalency  of  carbon.  Though  at  the  time  purely 
empirical,  it  had  the  effect  of  drawing  attention  to  many  formulae, 
which  proved  to  be  inaccurate  and  which  were  corrected  and 
simplified. 

Basicity  of  Acids.  The  halving  of  the  atomic  weights  of  the 
metals  and  the  introduction  of  the  two  volume  standard  of  molecular 
weights,  brought  out  clearly  the  relation  between  related  compounds. 
Acetic  acid  was  now  written  C2H402  and  silver  aoetate  C2H3AgO2, 
oxalic  acid  was  C2H2O4  and  silver  oxalate  C2Ag204.  The  basicity  of 
the  acid  appeared  as  the  number  of  hydrogen  atoms  replaceable  by 

1  Revue  scientifique  de  Quesneville,  1872. 


BASICITY   OF  ACIDS  29 

a  metal,  and  basic  water  necessarily  vanished.    The  series  were  written 
as  follows: 

Monobasic.  Dibasic.  Tribasic. 

Nitric  acid  NO3 .  H  Sulphuric  acid  S04 .  H2  Phosphoric  acid  P04 .  H3 

Formic,,      CHO,.H  Oxalic  „     C,O4.Ha  Citric  „     C01I-07.H3 

Acetic    „      CaHjOa.H 

Other  criteria  of  basicity  were  afterwards  added  by  Gerhardt  and 
Laurent.  It  was  no  longer  essential  that  an  acid  to  be  dibasic  should 
form  a  double  salt  with  two  different  bases,  as  defined  by  Liebig 
(p.  23).  An  acid,  if  monobasic,  formed  one  salt,  one  ether  and  one 
neutral  amide.  It  was  dibasic  if  it  formed  an  acid  and  neutral  salt, 
an  acid  and  neutral  ether  and  an  acid  and  neutral  amide,  as  well  as  an 
acid  chloride  containing  two  atoms  of  chlorine. 

Sulphuric  acid  and  oxalic  acid  were  consequently  dibasic  and 
formed  the  following  series  of  derivatives : l 

Oxalic  acid  C204 .  H.2  Sulphuric  acid  S04 .  H2 

Potassium  ethyl  oxalate  CjO^CjH,^  Potassium  sulphate  S04.K2 

Diethyl  oxalate  C.j04(C2H,)a  Potassium  bisulphate  S04 .  KH 

Oxamide  C^NH*),  Sulphovinic  acid  SO,  C2H5)H 

Oxamicacid  C2O3(NH2)H  Ethylic  sulphate  S04(C2fl5) 

The  radicals,  at  first  entirely  discarded  by  Gerhardt,  were  afterwards 
introduced  into  his  residues.  It  was  clear  that  in  a  substance  like 
acetic  ether  some  kind  of  fixity  existed  between  the  constituent 
parts,  acetic  acid  and  alcohol,  from  which  it  was  obtained  and  into 
which  it  could  easily  be  converted. 

Gerhardt's  System  of  Classification.  We  cannot  conclude  an 
account  of  Gerhardt's  contributions  to  organic  chemistry  without 
a  brief  reference  to  his  system  of  classification  which  appeared  in 
the  Precis  of  1844.  He  begins  by  defining  organic  chemistry  as  the 
chemistry  of  carbon  compounds,  and  proceeds  to  show  how  living 
nature  has  elaborated  the  most  complex  of  these  substances,  the 
simpler  ones  being  products  of  their  decomposition.  The  latter  may 
be  obtained  artificially ;  but  the  chemist  has  not  yet  succeeded  in 
building  up  the  former.  He  then  proceeds  to  explain  how  a  simple 
classification  may  be  obtained  by  arranging  compounds  having 
similar  properties  according  to  the  number  of  carbon  atoms  which 
they  contain,  and  which  he  termed  e'chelle  de  combustion.  In  the 
different  series  the  carbon  and  hydrogen  appear  in  the  ratio  of  one 
to  two.  Expanding  an  idea  which  Dumas  had  applied  to  the  organic 
acids,  and  Schiel  (1842)  to  the  alcohols,  Gerhardt  pointed  out  that  if 
E  stands  for  this  ratio,  then  marsh  gas  and  the  paraffin  series  are 
1  Laurent's  Chemical  Method  (Eng.  trans.),  61,  76,  and  225. 


30  ORGANIC   CHEMISTRY 


represented  by  72f  2,  the  alcohols  by  R*20,  and  the  acids  by  RO2,  &c. 
To  these  series  he  gave  the  name  of  corps  liomologms.  He  arranged 
all  organic  compounds  according  to  the  number  of  their  carbon 
atoms  on  the  same  rung  of  his  '  ladder  ',  and  called  it  a  family. 

Laurent's  Atoms,  Molecules,  and  Equivalents.     In  his  new 

system  Gerhardt  regarded  as  synonymous  the  terms  atom,  equiva- 
lent, and  volume,  by  which  he  understood  what  we  now  express  by 
the  word  molecule.  Laurent1  drew  clearer  distinctions  between 
them.  An  equivalent,  he  stated,  was  a  number  which  in  addition 
to  indicating  the  combining  weight  also  expressed  a  function  of 
an  element.  Thus,  the  quantity  of  different  bases  required  to 
neutralize  the  same  quantity  of  acid  is  its  equivalent.  The  quantity 
of  oxygen  which  replaces  hydrogen  in  a  compound  is  its  equivalent, 
but  this  does  not  imply  an  equal  number  of  atoms  ;  for  it  is  generally 
found  that  an  atom  of  oxygen  will  replace  two  atoms  of  hydrogen. 
These  equivalents  are  not  easy  to  determine  ;  for  different  groups  of 
elements  have  frequently  entirely  different  functions,  which  cannot 
be  directly  compared.  Manganese  in  the  manganous  salts  is  equiva- 
lent to  calcium  ;  in  the  manganates  it  is  equivalent  to  sulphur  (as  in 
the  sulpliates)  ;  and  in  the  permanganates  to  chlorine  (as  in  the  per- 
chlorates).  But  if,  he  said,  we  assume  that  equal  volumes  contain 
an  equal  number  of  atoms  (molecules),  the  atoms  become  strictly 
comparable  quantities  independent  of  the  function  of  the  elements 
they  contain.  In  reactions  with  chlorine  Laurent  observed  that  the 
atoms  taking  part  are  invariably  an  even  number.  Thus,  from  naph- 
thalene and  chlorine  new  products  are  formed  both  by  addition  and 
substitution  : 

C10H8  +  C12  =  C10H8C12 

C10H8-f2Cl2  =  C10H8Cl4 

C10H8  +  C12  =  C10H7C1  +  HC1,  &c. 

Adopting  the  suggestion  made  by  Ampere  that  the  atoms  of 
hydrogen  and  chlorine  are  divisible,2  he  concluded  that  the  elemen- 
tary gases  are  composed  of  two  atoms,  and  he  then  formulated  the 
distinction  between  atoms  and  molecules,  which  had  been  pointed 
out  so  clearly  forty  years  before  by  Avogadro  and  Ampere,  and 
which  we  still  accept.  When  atoms  of  hydrogen  and  chlorine  unite 
they  do  not  simply  become  attached  ;  but  the  molecules  of  hydrogen 
and  chlorine  first  divide  into  atoms  : 


= 

It  was  then  no  longer  necessary  to  distinguish,  as  Gerhardt  had 
1  Chemical  Method,  p.  7.  a  CJiemical  Method,  p.  65. 


LAUKENT'S  ATOMS,  MOLECULES,  AND  EQUIVALENTS    31 

done,  between  the  atoms  of  elementary  gases,  which  were  determined 
from  the  weight  of  single  volumes,  and  those  of  volatile  compounds, 
which  were  fixed  by  the  ratio  of  two  volumes  to  one  of  hydrogen. 
The  molecules  of  all  gases  could  now  be  brought  into  line  and  deter- 
mined on  the  two  volume  basis.  It  was  considerations  of  this 
nature,  as  well  as  the  law  of  even  numbers,  which  suggested  to 
Laurent  the  formula  Cy2  for  free  cyanogen,  instead  of  Cy,  and 
(CH3)2  for  that  of  the  newly  discovered  radical  methyl  in  place 
of  CH3. 

In  spite  of  views  thus  clearly  expressed  and  fully  endorsed  by 
both  Laurent  and  Gerhardt,  it  is  curious  to  find  in  Gerhardt's  treatise 
on  Organic  Chemistry,  the  first  volume  of  which  appeared  in  1853, 
the  reappearance  of  the  atomic  weights  and  barred  symbols  of  Berze- 
lius,  an  account  of  the  new  system  being  relegated  to  the  last  volume 
of  the  book.  The  strong  prejudice  which  still  existed  in  favour  of 
the  old  notation  is  evident  from  Gerhardt's  reply  to  Pebal  who  ques- 
tioned him  on  the  subject:  'My  book  would  never  have  found  a 
purchaser.'1  The  new  system  made  few  converts  until  after  the 
appearance  of  the  celebrated  brochure  of  Cannizzaro  in  1858,2  in 
which  the  principle  of  determining  molecular  weights  by  means  of 
the  vapour  density  was  systematically  laid  down  and  logically  carried 
through.  Until  that  time  the  equivalent  notation  of  Gmelin  became 
almost  universal. 

We  must  interrupt  the  narrative  at  this  point  in  order  to  follow 
the  fortunes  of  Berzelius  and  his  followers,  who  still  adhered  to  the 
radical  theory,  as  it  was  termed,  in  opposition  to  the  theory  of  sub- 
stitution. 

The  School  of  Berzelius.  After  a  masterly  criticism  of  Dumas' 
theoiy  of  types,3  Berzelius  drifted  entirely  away  from  the  French 
school,  which  now  claimed  Liebig  and  a  growing  number  of  the 
younger  German  chemists  among  its  adherents.  Nothing  could 
shake  his  faith  in  the  electro-chemical  theory  to  which  he  clung 
more  firmly  than  ever. 

Reviving  Lavoisier's  definition  of  a  radical,  Berzelius  wrote :  '  An 
oxide  cannot  be  a  radical.  The  veiy  meaning  of  the  word  indicates 
that  it  is  the  body  which  is  united  to  oxygen.  To  regard  a  radical 
as  an  oxide  would  be  equivalent  to  supposing  that  sulphurous  acid 
(S02)  is  the  radical  of  sulphuric  acid,  and  manganese  peroxide  (Mn02) 
that  of  manganic  acid/ 

1  Oswald's  Klassiker,  No.  30,  p.  66,  footnote. 

8  Nuovo  Cimento,  1868,  vol.  vii.  »  Jahresb.,  1840,  20,  260. 


32  OKGANIC  CHEMISTKY 

As  only  carbon,  hydrogen  and  nitrogen  could  form  part  of  an 
electro-positive  radical,  chlorine  as  well  as  oxygen  had  to  disappear 
from  the  radical.  Benzoyl  C14H1002  the  radical  of  benzoic  acid, 
originally  accepted  by  Berzelius,  was  now  replaced  by  'picramyl' 
CUH10,  and  the  chlorine  substitution  products  were  explained  as  chlo- 
rides of  hydrocarbon  radicals.  A  difficulty  was  presented  by  bodies 
which  contained  both  chlorine  and  oxygen.  In  such  cases  it  became 
necessary  to  double  and  sometimes  to  treble  the  original  formula. 
This  led  to  the  introduction  of  the  copula  or  conjunct  (Paarling),  an 
expression  borrowed  from  Gerhard  t,  but  employed  in  an  entirely 
different  sense.  Thus,  phosgene  was  written  C02  +  CC14,  that  is  a 
compound  of  oxide  of  carbon  united  to  the  conjunct,  chloride  of 
carbon.  For  the  same  reason  benzoyl  chloride  became  : 

2CUH1003  +  CUH10CJ6. 

Thus  Berzelius  continued  laboriously  to  construct  his  electro-chemical 
formulae  upon  a  foundation  which  every  moment  became  more 
insecure.1 

Chloracetic  acid  and  acetic  acid  were  at  first  regarded  by  Berzelius 
as  distinct  and  unrelated,  acetic  acid  being  the  trioxide  of  acetyl 
C4H6,  whereas  chloracetic  acid  was  oxalic  acid  united  to  the  conjunct, 
chloride  of  carbon, 

C2C16  +  C203  +  H20. 

The  complete  analogy  shown  to  exist  between  the  properties  of 
the  two  substances  (p.  20)  and  Melsens'  discovery  (1842),  that 
chloracetic  acid  can  be  converted  by  reduction  with  potassium 
amalgam  and  water  into  acetic  acid,  removed  this  shadowy  distinction, 
and  both  substances  now  appeared  as  conjugated  compounds  of  oxalic 
acid,  one  containing  the  radical  methyl  C2H6,  and  the  other  chloride 
of  carbon  CZCIQ  : 


The  replacement  of  hydrogen  by  chlorine  in  the  conjunct  did  not, 
according  to  Berzelius,  materially  affect  the  properties  of  the 
compound. 

Still  the  one  compound  was  virtually,  although  not  admittedly, 
a  substitution  product  of  the  other.  In  his  satisfaction  in  the  con- 
junct he  had  sacrificed  the  integrity  of  the  radical  and  tacitly  accepted 
the  principle  of  substitution. 

In  1845,  Hofmann  announced  the  discovery  of  the  chlorinated 

1  Jahresb.,  1839,  19,  375. 


THE   SCHOOL   OF  BERZELIUS  33 

and  brominated  anilines,1  and  later  the  iodo-,  cyano-  and  nitro-anilines, 
which  still  retained  the  basic  character  of  the  original  compound, 
although  the  property  was  weakened  in  proportion  to  the  amount 
of  hydrogen  replaced.  Berzelius  explained  the  change  by  repre- 
senting aniline,  as  he  represented  the  alkaloids,  as  ammonia  con- 
jugated with  a  hydrocarbon  C12H8  +  N£H6  ;  chloraniline  would  then 
be  ammonia  attached  to  the  conjunct  C12H6C12.  This  view  was 
at  first  accepted  by  Hofmann,2  but  he  soon  found  a  difficulty  in 
explaining  the  anomalous  behaviour  of  aniline  oxalate,  written 
N2H6(C12H8)H2C204,  which,  unlike  ammonium  oxalate,  refused  to 
yield  a  cyanogen  derivative  on  heating.  This  anomaly  is  removed 
if  aniline  is  an  amido  compound  ;  for  if  water  is  eliminated  from 
(C12H10)H4N2 .  H2C2O4  the  radical  phenyl  C12H10  must  be  destroyed.3 

Thus  aniline  and  its  derivatives  took  rank  as  phenyl  substitution 
products  of  ammonia. 

In  spite  of  the  rapidly  accumulating  evidence  in  favour  of  the 
substitution  theory,  Berzelius  never  relinquished  the  electro-chemi- 
cal theory  which  he  had  so  carefully  constructed  and  so  warmly 
defended. 

In  the  Treatise  of  1827  he  prophetically  wrote :  '  An  opinion 
long  held  often  brings  conviction  of  its  truth.  It  hides  from  us 
its  weaker  points,  and  thereby  renders  us  incapable  of  accepting 
adverse  views.' 4  Yet  nothing  could  be  more  unjust  than  to  infer 
that  the  views  of  Berzelius,  misleading  as  they  proved,  were  unpro- 
ductive. 

The  Researches  of  Frankland  and  Kolbe.  Two  disciples  of  his 
school,  Frankland  and  Kolbe,  contributed  between  the  years  1840 
and  1850  a  series  of  researches  of  supreme  importance  to  organic 
chemistry,  which  now  rank  among  the  classics  of  chemical  literature. 
Kolbe's  opinions  were  influenced  by  the  results  of  his  first  important 
investigation  (1844)  on  the  action  of  moist  chlorine  on  carbon  bisul- 
phide;5 for  it  is  here  that  the  galvanic  battery  is  first  mentioned  '  as 
perhaps  affording  the  experimenter  a  powerful  instrument  for 
disclosing  the  chemical  constitution  of  organic  compounds'.  The 
reaction  in  question  gave  rise  to  a  product,  which  was  decomposed 
by  potash,  forming  trichloromethylhyposulphuric  acid  (trichloro- 
methylsulphonic  acid).  By  the  successive  replacement  of  chlorine 

Cham.  Soc.  Memoirs,  1845,  2,  266  ;  Annalen,  1845,  53,  1 ;  54,  23. 

Annalen,  1848,  67,  172. 

Armstrong,  Memorial  Lecture,  Chem.  Soc.  J.,  1893,  655. 

Treatise  (1827),  vol.  iii,  p.  50. 

Annalen,  1845,  54,  145. 

PI.  I  D 


34  ORGANIC  CHEMISTRY 

by  hydrogen  Kolbe  obtained  a  series  of  compounds  which  in  the 
barred  notation  of  Berzelius  appeared  as  follows  : 


BO  +  C2-€13,  S  A 


The  compounds  were  represented  by  hyposulphuric  acid  conjugated 
with  methyl  or  substituted  methyl  radicals,  forming  a  parallel  series 
with  acetic  and  chloracetic  acids  : 


HO  +  C2H612,  C203 

HO  +  C2H2€1,CA 
HO  +  C2S3,C203 

*  The  following  facts/  he  concludes,  '  stand  in  a  certain  relation  to 
the  new  theory  of  substitution,  and  appear  at  first  sight  to  lend  it 
powerful  support.'1 

Whilst  formally  admitting  the  principle  of  substitution,2  Kolbe 
maintained  an  unshaken  faith  in  the  radicals  as  proximate  con- 
stituents of  organic  compounds,  which,  however,  can  undergo 
substitution  by  chlorine,  bromine,  amide,  nitrogen  peroxide,  &c.,  and 
the  object  of  many  of  his  polemical  writings  was  to  rehabilitate  the 
radical  theory  when  the  rival  type  theory  of  Gerhardt,  to  which 
reference  will  shortly  be  made,  threatened  to  replace  it. 

It  was  in  the  attempt  to  isolate  the  radicals  that  Kolbe  and 
Frankland  discovered  the  first  general  synthetic  methods  for  pre- 
paring the  paraffins.  As  far  back  as  1834  Liebig  had  suggested  the 
possibility  of  isolating  the  radicals,  and  even  suggested  a  method  for 
doing  so.3  In  1839  Lo"wig  announced  the  separation  of  ethyl  C4H5 
by  the  action  of  potassium  on  ethyl  chloride,4  but  it  is  improbable 
that  the  substance  he  describes  was  the  compound  in  question. 
By  acting  upon  ethyl  cyanide  with  potassium  Frankland  and  Kolbe 
hoped  to  remove  the  cyanogen  and  liberate  ethyl.5  A  gas  was 
evolved  which  corresponded  in  composition  to  the  radical  methyl 
C2H3.6  In  the  expectation  of  preparing  methyl  chloride  they  treated 
the  gas  with  chlorine,  and  obtained  a  compound  which  could  be 
liquefied  under  pressure,  and  had  the  composition  C4H5C1.  The 
substance  was  in  fact  ethyl  chloride,  and  the  hydrocarbon,  from 

1  Annalen,  1845,  54,  187.  a  Annalen,  1850,  75,  214. 

8  Annalen,  1834,  9,  15.  *  Pogg.,  Ann.,  1839,  45,  346. 

6  Annalen,  1848,  65,  269. 

6  This  was  explained  by  supposing  ethyl  C4H,«  to  break  up  into  methyl  C2H3 
and  olefiant  gas  C3H2. 


THE  RESEARCHES  OF  FRANKLAND  AND  KOLBE     35 

which  it  was  obtained,  ethane  ;  but,  by  some  alleged  discrepancy  in 
properties,  the  true  nature  of  the  reaction  escaped  them,  and  the 
chloride  was  described  as  a  conjugated  compound  of  methyl  with 
chloromethyl  CJg3.  C2B,€1. 

Other  hydrocarbons,  and  the  first  of  the  highly  interesting  class  of 
organo-metallic  compounds,  were  afterwards  obtained  by  Frankland,1 
who,  in  continuation  of  the  same  line  of  investigation,  substituted 
the  iodides  of  the  radicals  for  the  cyanides  and  zinc  for  potassium. 
By  the  action  of  zinc  on  ethyl  iodide  a  hydrocarbon  was  obtained, 
which  was  looked  upon  as  the  free  radical,  written  now  without 
barred  atoms,  C4H5,2  whilst  zinc,  ethyl  iodide  and  water,  when 
heated  under  pressure,  gave  a  hydrocarbon  which  was  identical  with 
that  previously  obtained  by  Frankland  and  Kolbe  from  ethyl  cyanide 
and  potassium,  and  was  consequently  methyl  C2H3.  Then  followed 
the  discovery  of  zinc  methyl,  zinc  ethyl,  &c.,  and  the  corresponding 
tin  and  mercury  compounds  and  their  oxides,  whilst  Lowig  and 
Schweizer3  succeeded  in  obtaining  the  antimony  derivatives,  Wanklyn* 
discovered  potassium  and  sodium  ethyl,  and  Friedel  and  Crafts,5 
silicon  ethyl. 

Not  the  least  important  of  the  contributions  made  by  Kolbe  and 
Frankland  to  organic  chemistry,  was  the  discovery  of  the  synthesis 
of  organic  acids  from  the  cyanides  of  the  radicals.6  This  research 
was  again  suggested  by  Berzelius'  views  on  the  constitution  of  acetic 
acid,  which  represented  it  as  oxalic  acid  conjugated  with  methyl. 

It  was  well  known  that  cyanogen  in  aqueous  solution  gradually 
changed  to  the  ammonium  salt  of  oxalic  acid  and  that  hydrocyanic 
acid  could  be  converted  by  alkalis  into  formic  acid,  which  was 
written  as  oxalic  acid  conjugated  with  hydrogen  H,  C203  +  HO. 

It  naturally  followed  that  methyl  cyanide  should  yield  methyl 
oxalic  acid,  i.  e.  acetic  acid,  and  so  with  the  other  cyanides.      The 
experimental  results  fully  corroborated   these   conclusions.     More- 
over,  it    brought    out    clearly   the    relationship  of    the    acids    as 
a  series  of  hydrocarbon  radicals  having  a  group  C203,  HO  in  common, 
which  translate  J  into  our  present  notation  corresponds  to  carboxyl : 
HO  +  H,  C203          Formic  acid 
HO  +  C2H3,  C  A     Acetic  acid 
HO  +  C4H5,  C^Og      Propionic  acid,  &c. 

1  Quart.  J.  Chem.  Soc.,  1849,  2,  263  ;  Annalen,  1849,  71,  171. 

2  Although  Kolbe  used  the  barred  atoms  in  his  formulae,  and  continued  to  do 
so  as  late  as  1850,  they  were  dropped  by  the  majority  of  chemists,  who  employed 
only  the  equivalent  notation  (C  =  6  ;  O  =  8,  &c.).    To  avoid  confusion  the  barred 
atom  is  henceforth  omitted  in  all  the  formulae. 

3  Annalen,  1850,  75,  315.  4  Annalen,  1858,  108,  67. 
5  Annalen,  1863,  127,  31.                         6  Annalen,  1848,  65.  288. 

D   2 


36  OKGANIC  CHEMISTKY 

In  direct  relation  to  this  research  stands  Kolbe's  investigation  into 
the  behaviour  of  the  fatty  acids  on  electrolysis,  which  resulted  in  the 
discovery  of  a  new  synthesis  of  the  paraffins.1  It  arose  out  of  an 
attempt  to  oxidize  the  oxalic  acid  of  the  acids  to  carbon  dioxide  in 
the  hope  of  liberating  the  radical  with  which  it  was  united  ;  or  in  his 
own  words,  '  Starting  from  the  hypothesis  that  acetic  acid  is  a  con- 
jugated compound  of  oxalic  acid  and  the  conjunct  methyl,  I  considered 
it,  under  these  circumstances,  not  at  all  improbable  that  electrolysis 
might  effect  a  separation  of  its  conjugated  constituents,  and  that  in 
consequence  of  a  simultaneous  decomposition  of  water,  carbonic  acid 
as  a  product  of  the  oxidation  of  oxalic  acid  might  appear  at  the  posi- 
tive, while  methyl,  in  combination  with  hydrogen,  viz.  as  marsh  gas, 
would  be  observed  at  the  negative  pole.'  Although  the  process  did 
not  take  place  quite  in  the  manner  anticipated,  the  success  of  the 
experiments  is  too  well  known  to  be  recapitulated  in  detail.  The 
radical  methyl  CZH3  (in  reality  ethane)  was  supposed  to  be  liberated 
from  acetic  acid,  and  valyl  C8H9  (in  reality  octane)  from  valeric  acid.2 
The  idea  of  the  copula  or  conjunct  which  was  requisitioned  by 
Berzelius  to  divide  or  duplicate  his  formulae  for  dualistic  purposes, 
received  from  Kolbe  a  rather  more  definite  signification  than  Berze- 
lius had  attached  to  it,  and  led  to  very  interesting  developments. 

If  all  the  organic  acids  are  conjugated  oxalic  acids,  it  follows  that 
the  character  of  the  radical  will  undergo  a  change  in  conformity  with 
this  view.  For  example,  the  original  acetyl  radical  C4H6  of  Regnault 
which  was  employed  to  show  the  relationship  between  aldehyde, 
acetic  acid  and  allied  compounds  (p.  16),  was  now  broken  up  by 
Kolbe  into  the  conjunct  methyl,  which  was  attached  to  carbon  thus, 
(C2H3)~C2.  The  radical  contained  two  pairs  of  carbon  equivalents,  and 
different  functions  were  ascribed  to  each.  It  was  the  pair  lying 
outside  the  radical  which  was  supposed  to  afford  the  point  of  attach- 
ment for  oxygen  and  chlorine.  Some  of  Kolbe's  formulae  appear  as 
follows : 3 

HO,(C2H3)~C2,O      Aldehyde 
HO,(C2H3)~C2,O3     Acetic  acid 

1  Quart.  J.  Chem.  Soc.,  1850,  2,  157  ;  Alembic  Club  Reprints,  No.  15 ;  Annalen, 
1849,  69,  257. 

3  It  is  a  curious  fact  that  the  formulae  of  both  hydrocarbons  (in  Kolbe's  nota- 
tion they  stood  for  C2H6,  C8H]8)  are  given  correctly,  though  transposed  into  the 
modern  form  they  would  stand  for  CH3  and  C4H9.  The  correspondence  is  acci- 
dental, and  arises  on  the  one  hand  from  the  use  of  the  double  molecular  formula 
for  the  acid,  and  on  the  other  from  the  fact  that  the  radicals  unite  in  pairs  and 
form  substances  having  molecular  weights  double  of  those  recognized  by  the 
author  of  the  memoir. 

3  See  footnote  2  on  previous  page. 


THE  RESEARCHES  OF  FRANKLAND  AND  KOLBE     37 

(C2H3)~C2,C13  Dichloro-hydrochloric  ether  (trichl  or  oe  thane) 

(C4H5)O  .  (C2Cl3rC2,O3     Trichloracetic  ether 

Acetamide 


(C2H3)~C2N  Methyl  cyanide 

In  this  way  methyl  was  recognized  as  an  integral  part  not  only  of 
acetic  acid,  but  of  marsh  gas  (C2H3)H,  which  it  yielded  on  distillation 
with  lime,  and  of  cacodyl  oxide,  written  (C2H3)2As,0,  which  it  formed 
on  heating  the  potassium  salt  with  arsenious  oxide.  It  explained,  more- 
over, why  the  last  equivalent  of  hydrogen  in  chloral  HO,  (C2C13)C.,,O 
was  not  replaced  by  chlorine.  The  same  system  was  applied  to  other 
acids,  henzoic  acid  and  its  derivatives  being  represented  by  oxalic  acid 
conjugated  with  the  radical  phenyl  C12H5: 

HO.(Ci2H5)~C2,O3  Benzoic  acid 

HO,(C12  1  ^  rC2,03     Nitrobenzoic  acid 

(  H 

HO,(C12  \  _  1-  rC9,O3     Amidobenzoic  acid 
I  JMH2 

For  the  same  reason  that  marsh  gas  became  the  hydride  of  methyl, 
benzene  appeared  as  the  hydride  of  phenyl  (C12H5)H,  and  phenol  as 
its  oxyhydrate  HO  .  (G12H.5)0.1  In  this  way  Kblbe  sought  to  rehabi- 
litate the  compound  radical  : 

The  constitution  attached  to  cacodyl  oxide  was  later  extended  to 
cacodyl  and  the  organo-metallic  compounds  generally  in  which  the 
radicals  appeared  as  the  conjuncts  of  the  metals.  Kolbe  was,  indeed, 
the  first  to  interpret  correctly  the  constitution  of  cacodyl  to  the 
extent  of  regarding  it  as  arsenide  of  methyl  (C2H3)2~As. 

Frankland  dissented  from  this  view.  It  was  generally  admitted 
that  the  saturation  capacity  of  a  substance  was  retained  in  a  conju- 
gated compound.  Oxalic  acid  has  the  same  saturation  capacity  in 
the  free  state  as  when  conjugated  with  the  radical  methyl  C2H3  in 
acetic  acid.  This  was  not  the  case  with  the  metal  in  the  organo- 
metallic  compounds.  Cacodyl  in  cacodylic  acid,  which  is  the  highest 
oxidation  product,  is  only  united  to  three  atoms  of  oxygen  instead 
of  five  as  in  arsenic  acid,  to  two  in  antimony  ethyl  and  to  only 
one  in  tin  ethyl.  He  preferred  to  represent  these  compounds  as 
substitution  products  of  the  metallic  oxides: 

1  Annakn,  1850,  76,  1. 


38 


Inorganic  types. 


As-{  0 
0 


As- 


O 
O 
0 
IOJ 
ZnO 


Sb- 


0 


0) 

O\ 

O 

Sb- 

0 

0 

0 

0\ 

0 

Sb 

0 

0 

0 

SnO 

Sn 


{o} 


ORGANIC   CHEMISTRY 

Organo-metaHic  derivatives. 


As  -1  C2H3  j-      Cacodyl  oxide 
O 


Cacodylic  acid 


Zn(C2H3)         Zincmethylium 

(  O  H   1 
Zn  <     *    3  >      Oxide  of  Zincmethylium 

Sb    cX  [      Stibethine 
1  C4H5  j 


Sb- 


Binoxide  of  Stibethine 


Sb, 


Oxide  of  Stibethylium 


C4H5 
0 
Sn(C4H6)        Stanethylium 


4    5  |      Oxide  of  Stanethylium 
*{?"•} 


Iodide  of  Hydrargyro- 
methylium 

It  was  in  this  memoir1  that  Frankland  drew  attention  to  the 
regularity  subsisting  between  the  number  of  the  different  kinds 
of  atoms  which  are  found  in  combination  with  the  same  element. 
This  was  the  first  announcement  of  the  doctrine  of  valency  or 
atomicity,  as  it  was  then  called,  which  will  be  referred  to  pre- 
sently (p.  50). 

1  Phil.  Trans.,  1852,  142,  417. 


KOLBE'S   VIEWS  ON   CONSTITUTION  39 

Kolbe's  Views  on  Constitution.  This  relation  of  the  organo- 
metallic  compounds  to  the  oxides  of  the  metals,  which  Frankland  first 
pointed  out,  suggested  to  Kolbe  a  further  modification  of  his  theory 
of  conjugated  compounds.1  As  cacodylic  acid  HO(C2H3)2As03S  may 
be  derived  from  arsenic  acid  3HO,AsO5  by  replacing  two  atoms  of 
oxygen  by  two  methyl  radicals,  so  carbonic  acid  may  be  regarded  as 
the  mother  substance  of  the  organic  acids  in  which  part  of  the 
oxygen  is  replaced  by  hydrogen  or  radicals  : 

2HO.C2O4  HO.HC2O3  HO.C2H3.C2O3,       &c. 

Carbonic  acid.  Formic  acid.  Acetic  acid. 

This  was  a  counter-stroke  delivered  by  Kolbe  at  the  artificial  in- 
organic types,  as  he  regarded  them,  of  Gerhardt's  new  theory  which 
had  just  appeared  (see  p.  44).  Carbonic  acid,  the  raw  material  of 
vegetable  synthesis,  was  on  the  contrary  a  natural  type  from  which, 
as  by  the  vital  process,  complex  derivatives  may  be  obtained. 

In  order  to  explain  the  difference  of  basicity  between  carbonic 

acid  and  the  fatty  acids,  the  group  C204  in  carbonic  acid  was  split 

into  two  (C202),O2,  and  the  basicity  was  made  to  depend  on  the 

number  of  extra-radical  oxygen  atoms.     The  above  formulae  became 

2HO  .  (C202),02        HO  .  H(CA),0        HO  .  (CjHgXC  A),O 

Carbonic  acid  with  its  two  extra  radical  oxygen  atoms  is  dibasic, 
whereas  formic  and  acetic  acids,  with  only  one,  are  monobasic.  By 
replacing  the  last  extra-radical  oxygen  by  hydrogen  or  a  radical  the 
neutral  aldehydes  and  ketones  result: 


Formaldehyde  Acetaldehyde.  Acetone. 

(then  unknown). 

If  in  these  more  oxygen  is  substituted,  the  alcohols  and  finally  the 
hydrocarbons  are  obtained  : 

HO.C2H3,0 

Methyl  alcohol.  Ethyl  alcohol.  Ethyl  hydride. 

The  curious  part  played  by  the  molecules  of  water,  which  sometimes 
appear  upon  the  scene  and  again  vanish,  is  due  to  the  insignificant 
role  assigned  to  them  by  Berzelius  and  his  school. 

However  fantastic  Kolbe's  formulae  may  now  appear,  the  system 
was  in  so  far  successful  that  it  enabled  him  to  foretell  the  existence 
of  many  unknown  compounds,  some  of  which,  though  not  all, 
have  since  been  obtained.  Thus,  formaldehyde  was  predicted,  and 

1  Annalen,  1857,  101,  257  ;  1860,  113,  293  ;  Ostwald's  Klassiker,  No.  92. 
1  In  these  and  subsequent  memoirs  Kolbe  discarded  th<s  barred  atoms. 


40  ORGANIC   CHEMISTRY 

also  the  secondary  and  tertiary  alcohols.  '  For,'  says  Kolbe,  'suppose 
that  we  introduce  into  the  alcohols  in  place  of  one  or  two  atoms  of 
hydrogen  the  same  number  of  methyl,  ethyl,  &c.,  atoms  in  the  same 
manner  (as  acetone  is  derived  from  aldehyde),  wo  shall  obtain  new 
alcohol  compounds  of  the  following  constitution.' 

Normal  alcohol  HO  {  °aJJ= 


Monomethyl  alcohol      HO  \  C2H 


3 
H 


Dimethyl  alcohol  HO  \  C2H 


(C2H3 
Methyl  ethyl  alcohol      HO  \  C2H3 


c,,o 


c,,o 


I 

'The  monomethyl  alcohol  will  be  isomeric,  not  identical  with 
propyl  alcohol,  and  dimethyl  alcohol  will  be  isomeric  with  butyl 
alcohol.' 

Two  years  later  the  first  of  these  predictions  was  verified  by  Friedel, 
who  isolated  secondary  propyl  alcohol,  and  the  second  by  Butlerow  in 
1864,  who  prepared  tertiary  butyl  alcohol.  They  agreed  in  nearly 
every  particular  with  the  properties  foretold  by  Kolbe. 

'  These  compounds  will  probably  form,  with  the  hydracids,  halogen 
compounds  like  ethyl  chloride,  also  sulphur  compounds  and  mercap- 
tans,  and  with  sulphuric  acid,  sulphuric  ethers  ;  but  those  compounds 
which  are  combined  like  the  dimethyl  alcohols  will  not  be  oxidized 
to  aldehydes  and  acids,  like  the  normal  alcohols,  as  the  two  free 
hydrogen  atoms,  which  in  the  normal  alcohols  are  attacked,  are 
missing.  Nor  can  the  monomethyl  alcohols  which  still  retain  a  free 
hydrogen  atom  be  converted  into  acids,  but  by  the  same  process  of 
oxidation  which  yields  aldehydes  in  the  case  of  normal  alcohols  will 
convert  the  monomethyl  alcohols  into  acetone.' 

We  must  now  pick  up  the  thread  of  the  narrative  where  we  dropped 
it  to  follow  the  fortunes  of  the  radical  theory. 

The  standard  of  volumes  adopted  by  Gerhardt  and  Laurent  for 
determining  molecular  weights  served  its  purpose  admirably  by 
bringing  together  compounds  which  were  related  to  one  another, 
but  gave  no  information  about  their  structure.  The  doctrine  of 
residues  in  its  original  simplicity  could  not  satisfy  the  aspirations 
of  chemists  in  face  of  the  powerful  testimony  which  the  researches  of 
Frankland  and  Kolbe,  Hofmann  and  many  other  chemists,  had 
brought  in  support  of  the  radical  theory. 


WILLIAMSON'S   RESEARCHES  ON  ETHER  41 

Williamson's  Researches  on  Ether.  It  was  at  this  critical 
period  in  the  history  of  the  science  that  a  short  and  unpretentious 
memoir  appeared,  which  gave  an  unexpected  turn  to  the  current  of 
chemical  thought.  This  was  Williamson's  research  on  etherification, 
which  was  first  read  at  the  meeting  of  the  British  Association  at 
Edinburgh  in  1850.1  It  is  difficult  to  embrace  in  a  sentence  the 
far-reaching  consequences  which  followed  its  publication.  In  the 
first  place  it  settled  the  vexed  question  of  the  relation  of  alcohol  to 
ether  ;  secondly,  it  introduced  a  new  and  important  synthetic  pro- 
cess ;  it  showed,  further,  how  chemical  methods  might  be  employed 
in  determining  molecular  weights  ;  but  above  all  it  reconciled  the 
two  contending  schools  of  thought  by  welding  together  the  radical 
theory  with  Dumas'  theory  of  types. 

The  constitution  of  alcohol  and  ether  had,  as  we  have  seen,  received 
various  interpretations.  Berzelius  regarded  them  as  oxides  of 
different  radicals,  Liebig  formulated  ether  as  the  oxide  of  ethyl  and 
alcohol  as  its  hydrate,  Gerhardt  in  1844  wrote  their  formulae  C2H60 
and  C4H10O  from  the  value  of  their  vapour  densities,  and  Laurent  in 
1846  explained  their  relation  by  comparing  them  to  potassium  hydrate 
and  potassium  oxide,  as  the  hydrate  and  oxide  of  ethyl  (=  Et).2 

KHO  EtHO 

KKO  EtEtO. 

In  1850  Williamson  investigated  the  action  of  ethyl  iodide  upon 
potassium  ethylate  in  the  hope  of  replacing  the  potassium  by  ethyl 
and  so  forming  a  new  ethylated  alcohol. 

The  experiment  gave  entirely  unexpected  results  ;  for,  in  place  of 
alcohol,  he  obtained  ordinary  ether.  He  recognized  the  importance 
of  the  result,  explained  by  means  of  it  the  formation  of  ether,  and 
demonstrated  the  correctness  of  his  conclusions  in  a  series  of  brilliant 
experiments.  Williamson  saw  at  once  the  application  of  Laurent's 
and  Gerhardt's  views,  which  he  was  one  of  the  first  to  adopt, 
formulating  the  reaction  thus  : 


Kolbe  strongly  opposed  this  view  and  represented  the  reaction  as 
follows  : 

C4H5OKO  +  C4H5I  =  2  (C4H50)  +  KI; 

in  which,  using  the  equivalent  notation,  potassium  alcoholate  appears 
as  a  compound  of  potash  and  ether.     Substituting  methyl  iodide  for 

1  Quart.  J.  Chem.  Soc.,  1852,  4,  229  ;  Al^nbic  Club  Reprints,  No.  16. 
1  Chemical  Method,  p.  75. 


42  ORGANIC   CHEMISTRY 

ethyl  iodide,  methyl  ether  and  ethyl  ether  should  be  formed,  sup- 
posing the  latter  view  to  be  correct,  whilst,  according  to  Williamson's 
theory,  methyl  ethyl  ether  should  be  formed.  It  was  the  second  re- 
action which  occurred. 

The  experiments  clearly  demonstrated  that  ether  is  derived  from 
alcohol  by  replacing  one  atom  of  hydrogen  by  ethyl,  and  conse- 
quently that  it  possesses  a  larger  molecule. 

It  now  remained  to  explain  the  formation  of  ether  from  alcohol 
and  sulphuric  acid. 

The  formation  of  ether  by  heating  a  mixture  of  alcohol  and  sul- 
phuric acid  is  so  simple  an  operation  that  it  seems  not  a  little 
remarkable  that  more  than  two  centuries  elapsed  before  the  obscurity 
which  enveloped  this  reaction  was  finally  removed.  As  the  study  of 
this  subject  and  the  discussions  which  rival  theories  called  forth 
engaged  chemists  from  the  very  inception  of  organic  chemistry,  it 
will  not  be  entirely  out  of  place  to  trace  the  phases  of  its  development. 
The  first  method  for  preparing  ether  is  ascribed  to  Valerius  Cordus 
in  1540,  who  called  it  oleum  vitrioli  dulcc,  the  name  being  changed  to 
etiier  by  Frobenius  in  1730.  The  compound  was  formed  by  heating 
a  mixture  of  alcohol  and  strong  sulphuric  acid.  Fourcroy  and 
Vauquelin  explained  the  reaction  by  supposing  that  alcohol  loses  a 
molecule  of  water.  This  agreed  with  the  etherin  theory  and  with 
Liebig's  later  view.  The  explanation  was,  however,  open  to  criticism. 
Other  dehydrating  agents,  like  potash  and  baryta,  effected  no  change 
of  this  kind,  and  when  it  was  afterwards  pointed  out  that  water 
distilled  with  the  ether,  it  was  difficult  to  conceive  how  sulphuric 
acid  could  act  by  reason  of  its  affinity  for  water  if  it  parted  with  it 
in  the  process.  Dabit  discovered  that  the  first  action  of  the  sulphuric 
acid  on  alcohol  at  the  ordinary  temperature  was  the  formation  of 
a  new  acid,  which  was  not  precipitated  by  barium  salts.  It  was 
termed  sulphovinic  acid  by  Serturner,  who  studied  it  more  carefully. 
Then  followed  the  discovery  that  the  contents  of  the  vessel  after 
distilling  off  the  ether  could  be  used  for  the  preparation  of  fresh 
quantities  of  the  latter  by  adding  alcohol,  an  observation  upon  which 
Boullay,  the  father  of  Dumas'  colleague,  founded  the  present  con- 
tinuous process.  The  first  clear  experimental  evidence  as  to  the 
nature  of  this  curious  and  coniplex  reaction  is  due  to  Hennel,  an 
English  apothecary.  He  proved  that  the  formation  of  sulphovinic 
acid  is  essential  to  the  process.  In  the  first  place  he  found  by  dis- 
tilling equal  quantities  of  sulphuric  acid  and  alcohol  that,  as  the 
ether  distils,  the  quantity  of  free  sulphuric  acid  increases,  whilst  that 
of  the  sulphovinic  acid  decreases.  If,  on  the  other  hand,  the  mixture 


WILLIAMSON'S   RESEARCHES  ON  ETHER  43 

is  first  diluted  with  water,'  nothing  but  alcohol  passes  over,  and 
sulphuric  acid  remains  in  the  distilling  vessel.  He  further  showed 
that  on  heating  sulphovinic  acid,  as  free  as  possible  from  alcohol  or 
water,  a  certain  quantity  of  ether  distils.1  Berzelius,2  in  his  Jahres- 
bericht  for  1829,  attributes  to  Hennel  the  view  that  ether  is  formed 
by  the  action  of  alcohol  on  sulphovinic  acid,  and  since  the  latter,  as 
Hennel  first  showed,  is  a  compound  of  olefiant  gas  with  sulphuric 
acid,  ether  must  be  a  compound  of  olefiant  gas  with  alcohol,  a  con- 
clusion which  bears  a  striking  resemblance  to  the  modern  view ;  but 
there  is  nothing  in  Kennel's  original  paper  which  we  can  find  in 
support  of  this  statement. 

Hennel  rather  suggests  that,  on  heating  sulphovinic  acid,  olefiant 
gas  is  separated  in  a  condition  which  enables  it  to  unite  with  one 
proportion  of  water  to  form  ether  and,  when  diluted,  with  a  larger 
proportion  of  water  to  form  alcohol.  He  subsequently  expanded  his 
theory  as  follows:  When  sulphuric  acid  and  alcohol  are  mixed 
sulphovinic  acid  and  water  are  formed,  the  latter  diluting  a  portion 
of  the  free  sulphuric  acid  present.  On  heating  the  sulphovinic  acid, 
it  is  the  water  of  this  dilute  acid  which  attracts  the  sulphuric  acid 
of  the  sulphovinic  acid,  and  enables  it  to  split  up  into  ether  and 
sulphuric  acid.  It  should  be  remembered  that  the  composition  of 
sulphovinic  acid,  as  determined  by  Serullas  (1829),  and  later  by 
Liebig  and  Wohler  (1833),  was  represented  as  an  acid  sulphate  of 
ether,  and  written 

C4H10O.S03  +  H2O.S03. 

Liebig,  as  the  result  of  a  series  of  careful  experiments,  showed  that 
sulphovinic  acid  does  not  change  below  a  temperature  of  124°,  but 
above  that  temperature  it  decomposes  into  ether,  sulphuric  acid,  and 
sulphuric  anhydride.  He  attempted  to  reconcile  these  facts  with 
Kennel's  views  in  the  following  manner:  the  alcohol  on  falling 
into  the  hot  sulphuric  acid  lowers  the  temperature  below  124°  at  the 
surface  of  contact,  forming  sulphovinic  acid  and  water,  which  dilutes 
the  sulphuric  acid  around  it.  The  sulphovinic  acid  then  diffuses  into 
the  hotter  liquid  where  it  decomposes  into  ether,  which  distils,  and 
sulphuric  anhydride  which  combines  at  once  with  the  water  of  the 
dilute  acid,  regenerating  concentrated  acid,  and  is  thus  capable  of 
uniting  with  fresh  alcohol.  The  simultaneous  distillation  of  water 
was  accounted  for  by  supposing  that  the  ether  vapour  carries  with  it 
water  vapour  much  in  the  same  way  that  a  high  boiling  volatile 
liquid  may  be  distilled  in  steam.  Mitscherlich,  however,  found  that 
by  passing  alcohol  vapour  into  the  mixture,  so  that  no  lowering  of 
1  Phil.  Trans.,  1826,  2,  240.  '-  Jahresb.,  1829,  9,  294. 


44  ORGANIC  CHEMISTRY 

temperature  occurred,  the  formation  of  ether  was  not  interrupted, 
and  both  he  and  Berzelius,  and  afterwards  Graham,  explained  the 
peculiar  effect  of  the  sulphuric  acid  as  a  catalytic  or  contact  pheno- 
menon, by  which  they  understood  such  a  reaction  as  occurred  in  the 
presence  of  a  substance  which  itself  underwent  no  change,  and  for 
which  no  satisfactory  explanation  was  forthcoming.1 

The  composition  of  ether  being  now  clearly  established,  William- 
son turned  the  fact  to  account  in  order  to  explain  the  production  of 
ether  from  alcohol  and  sulphuric  acid. 

The  explanation  is  the  one  we  still  adopt.  The  process  occurs 
in  two  stages.  Sulphovinic  acid  and  water  are  first  produced, 
and  the  sulphovinic  acid  reacting  with  a  fresh  quantity  of  alcohol 
forms  ether  and  regenerates  sulphuric  acid.  Ether  and  water  distil 
whilst  the  sulphuric  acid  is  free  to  react  with  fresh  alcohol,  and 
repeat  the  same  cycle  of  changes.  Williamson  confirmed  these  views 
by  showing  that  mixed  ethers  could  be  readily  obtained  by  the  use 
of  two  different  alcohols,  and  prepared  in  this  way  a  series  of  com- 
pounds containing  from  three  to  seven  carbon  atoms. 

In  reviewing  his  results  he  points  out  that  compounds  like 
alcohol,  ether,  acetic  acid,  and  its  hypothetical  anhydride  may  be 
regarded  as  water  in  which  one  or  two  hydrogen  atoms  are  replaced 
by  the  radicals  ethyl  and  otliyl  (oxygen  ethyl): 

C2H5Q  C2H5Q  (C2H30)  (C2H:50)0 

H°>  C2Hr,0'  H°'  (C2H30)a 

Alcohol.  Ether.  Acetic  acid.  Acetic  anhydride. 

This  memorable  paper,  which  proved  so  fruitful  in  results  and 
provided  such  a  powerful  stimulus  to  future  research,  concludes 
with  the  following  words  :  '  The  method  here  employed,  of  stating 
the  rational  constitution  of  bodies  by  comparison  with  water, 
seems  to  me  to  be  susceptible  of  great  extension,  and  I  have  no 
hesitation  in  saying  that  its  introduction  will  be  of  service  in 
simplifying  our  ideas,  by  establishing  a  uniform  standard  of 
comparison  by  which  bodies  may  be  judged  of.'2 

Gerhardt's  discovery  of  the  acid  anhydrides,  in  the  same  year,  by 
heating  the  acid  chlorides  with  their  sodium  salts,  amply  justified 
Williamson's  conclusions. 

Gerhardt's  New  Theory  of  Types.  In  the  following  year,  1853, 
Gerhardt3  published  his  new  theory  of  types,  already  foreshadowed 
in  a  memoir  by  Chancel  and  himself  on  The  Constitution  of  Organic 

1  Jahresb.,  1835,  15,  243.  2  Quart.  J.  Chcm.  Soc.,  1852,  4,  239. 

3  Ann.  Chim.  Phys.,  1853.  37,  332. 


GERHARDT'S   NEW   THEORY   OF  TYPES  45 

Compounds,  which  appeared  in  the  Revue  Scicntifiqite  for  1851.  It 
was  a  direct  outcome  of  Williamson's  memoir  on  ether,  though 
unacknowledged  at  the  time  of  its  publication.1 

To  understand  this  development  we  must  recall  a  few  facts.  In 
1849  Wurtz  had  obtained,  by  the  action  of  potash  on  cyanic  and 
cyanuric  ethers,  bases  closely  allied  in  smell  and  basic  characters  to 
ammonia,  which  he  compared  to  ammonia  wherein  an  atom  of 
hydrogen  was  replaced  by  the  radicals  methyl,  ethyl,  and  amyl.3 
Although  the  existence  of  such  compounds  had  been  foretold  ten 
years  earlier  by  Liebig,  it  was  the  first  successful  attempt  to 
introduce  radicals  into  ammonia.  This  interesting  fact  is  recalled 
by  Liebig  himself  in  a  note  to  Wurtz's  paper  in  the  Annalen.3 

'  If  one  considers  the  combination  NH2  or  amide  as  a  compound 
radical,  which  possesses  the  properties  of  radicals  as  opposed  to  those 
of  acid  radicals,  it  is  clear  that  ammonia  is  the  hydrogen  compound 
of  a  basic  radical,  which  is  similar  in  composition  to  hydrocyanic 
acid,  but  is  the  reverse  in  properties.  Hydrogen  cyanide  is  an  acid, 
hydrogen  amide  has  alkaline  properties,  a  difference  due  to  the 
characters  of  the  radicals  which  they  contain.  .  .  .  Now  we  know 
that  amide  is  capable  of  replacing  equivalent  for  equivalent  the 
oxygen  of  many  organic  acids,  and  we  find  that  the  new  com- 
pounds thus  produced  have  altogether  lost  the  nature  of  acids, 
being  indifferent  in  their  chemical  character.  .  .  .  If  in  the 
oxides  of  methyl  and  ethyl,  the  oxides  of  two  basic  radicals,  we 
were  able  to  substitute  one  equivalent  of  amide  for  oxygen, 
there  cannot  be  the  slightest  doubt  that  we  should  obtain  compounds 
perfectly  .similar  in  their  behaviour  to  ammonia.  Expressed  in 
a  formula  a  compound  C4H5  +  NH2  =  E  +  Ad  must  have  basic 
properties.' 

The  character  which  Wurtz  attached  to  these  compounds  was 
soon  afterwards  confirmed  by  Hofmann,  who  obtained  what  are 
known  as  the  primary,  secondary,  and  tertiaiy  bases  by  the  action  of 
the  iodides  of  the  alcohol  radicals  on  aniline  and  ammonia.4 

The  organic  phosphorus  compounds  which  Paul  Thenard  had 
discovered  in  1845  now  received  an  analogous  interpretation.  In 
addition  to  these  new  classes  of  compounds,  the  acid  chlorides  had 
been  prepared  by  Cahours5  in  1845,  and  the  anilides  and  other 
amides  by  Gerhardt  and  Chiozza  6  in  1853. 

1  Vie  de  Gerhardt,  p.  412. 

2  Compt.  rend.,  1848,  26,  368;  27,  241;   1849,  28,  223,  323;  29,  169,  186,  203; 
Annalen,  1849,  71,  326. 

3  Annalen,  1849,  71,  347.  *  Annalen,  1850,  73,  91 ;  1851,  79,  16. 
6  Compt.  rend.,  1845,  21,  145;  1847,  25,  892.  «  Compt.  rend.,  1853,  37,  86. 


46 


ORGANIC  CHEMISTKY 


All  these  groups  of  compounds  were  now  referred  by  Gerhardt  to 
four  types.  In  expounding  his  theory  he  says  :  *  I  do  not  attach  to 
these  so-called  rational  formulae,  which  give  the  molecular  constitu- 
tion of  chemical  compounds,  any  exaggerated  value,  because  they  are 
in  fact  only  the  expression  of  a  partial  truth,  which  in  a  more  or  less 
complete  fashion  includes  a  certain  number  of  chemical  changes. 
Such  formulae,  however,  appear  to  me  to  have  their  use,  for  they 
may  exert  a  happy  influence  on  the  development  of  the  science,  if 
they  are  viewed  from  the  same  standpoint  and  accord  well  together.5 

The  four  types  which  he  proposes  are  water,  H20,  hydrogen,  H2, 
hydrochloric  acid,  HC1,  and  ammonia,  NH3.  Each  vertical  series  is 
derived  from  the  type  by  replacing  the  hydrogen  by  radicals  : 


H 


Type. 


H 


a) 

Type. 

1   TT      \ 

*&} 


H 


Type. 


N 


N 


Ethyl  hydride. 


Ethyl  chloride. 

C2H30 


Ethyl  alcohol. 


Diethyl.        Acetyl  chloride. 


CH0 


Aldehyde. 

C.H30 
CH, 


C7H50 J 
Clf 

Benzoyl  chloride. 

ON) 


Ethyl  ether. 

C2H3OJ0 

Acetic  acid. 

C2H30 


HI 

H 

H, 

Type. 

CH5 

"H 

H 

Ethylamine. 

C2H5) 
C2H5    N 
H, 

Diethylamine. 


C2H5 


- 


Acetone.         Cyanogen  chloride.     Acetic  anhydride. 


C2H5 
C2H5 

Triethylamine. 

C2H30) 
H 
H 

Acetamide. 


They  were  in  a  sense  mechanical  rather  than  chemical  types,  for 
the  members  of  one  type  were  connected  together  more  in  outward 
form  than  in  properties ;  but  the  typical  formulae  served  admirably 
to  express  double  decompositions,  to  indicate  the  relation  which  the 
function  of  an  element  bears  to  its  position  in  the  type,  and  finally,  to 
explain  cases  of  isomerism. 

Inorganic  compounds  were  also   constructed   on   the   system  of 

types,  nitric  acid  being  represented  by  Williamson  as      -, 
which  Gerhardt  added  Deville's  nitric  anhydride  ,*  I  0. 


CONDENSED   TYPES  47 

Condensed  Types.  In  developing  his  views  on  the  constitution 
of  the  ethers,  Williamson  had  already  introduced  the  idea  of  the 
condensed  water  type.  He  pointed  out  that  it  may  be  usefully 
employed  in  formulating  the  action  of  potash  on  the  organic  ethers.1 


In  this  equation  the  two  atoms  of  hydrogen  in  the  double  molecule 
of  potash  are  replaced  by  the  group  CO.  Williamson  recognized  in 
this  the  existence  of  what  we  now  term  a  multivalent  radical,  which 
was  then  called  by  analogy  with  the  polybasic  acids,  a  polybasic 
radical.  The  group  CO  was  therefore  dibasic,  or,  according  to 
Gerhardt,  diatomic.  The  group  S02  was  regarded  in  the  same  light, 
the  formula  for  sulphuric  acid  being  derived  from  a  condensed  water 
type  of  two  molecules  and  written 


SO, 

H; 


}o2. 


Odling  extended  the  idea  to  other  inorganic  and  organic  acids, 
and  to  the  metals  themselves  : 


Type.  Acetic  acid.  Nitric  acid. 

H2i0  OAU  S04o 

HJ°«  H2}°*  H2/°2 

Type.  Oxalic  acid.  Sulphuric  acid. 


Type.  Citric  acid.  Phosphoric  acid. 

Wnrtz's  Researches  on  Giycol.  In  1854  Williamson  and  Kay 
obtained  orthoformic  ether  by  the  action  of  sodium  ethylate  on 
chloroform : 3 

CH)      3Na     )0=       CH 
C13  J        C2H5  /        (C2H5)3 

This  was  the  first  example  of  a  tribasic  hydrocarbon  radical. 
About  the  same  time  Berthelot  was  engaged  in  the  investigation  of 
glycerine,  and  found  that  it  unites  in  three  distinct  proportions  with 
acids,  forming  acetins,  stearins,  and  chlorhydrins,  &c.  He  concluded 

1  The  Cftemical  Gazette,  1851,  9,  334;  Alembic  Club  Reprints,  No.  16,  46, 
3  Quart.  J.  Chem.  Soc.,  7,  1. 
3  Proc.  Roy.  Soc.,  1854,  7,  135. 


48  ORGANIC  CHEMISTRY 

that  glycerine  bore  the  same  relation  to  phosphoric  acid  that  alcohol 
does  to  nitric  acid  : 


Wurtz  quickly  perceived  that  a  compound  intermediate  between 
alcohol  and  glycerine  should  exist,  derived  from  a  double  water  type, 
and  containing  a  dibasic  radical.  Before  long  he  had  supplied  the 
necessary  link  by  the  discovery  of  glycol  :  l 

C2H 


He  prepared  the  compound  from  ethylene  iodide  and  silver  acetate, 
which,  on  heating  together,  yield  ethylene  acetate  and  silver  iodide. 
Using  the  typical  formulae,  the  equation  appears  thus  : 


Ethylene  acetate  on  hydrolysis  with  potash  forms  glycol  : 

^2^4  If),  OKTJO  _  C2II4  I  o    ,  o^HsO  )  ~ 
(C2H302)2  /  U2  +  H2  /  U-  +  K  p 

Mixed  Types.  The  use  of  condensed  types  was  shortly  followed 
by  the  introduction  of  Kekule's  mixed  types*  which  he  set  forth  in 
a  paper  On  the  so-called  Conjugated  Compounds  and  the  Theory  of  Poly- 
atomic Radicals.  Kekule's  object  was  to  explain  the  constitution  of 
Gerhardt's  new  conjugated  radicals,  that  is,  the  old  conjugated  com- 
pounds which,  in  their  new  typical  garb,  played  the  part  of  substituted 
radicals.  Benzenesulphonic  acid,  sulphobenzoic  acid,  and  sulphovinic 
acid  were  written 


C7H4(S02X>  I  Q2        C2H5(S02)0  )  Q 

Benzenesulphonic  acid.     Sulphobenzoic  acid.         Sulphovinic  acid. 

Benzenesulphonic  acid  may  be  represented,  according  to  Kekule,3 
as  derived  from  the  two  types  of  hydrogen  and  water, 

H  e 


1  Ann.  Chim.  Phys.,  1859  (3),  55,  400. 

3  Annalen,  1857,  104,  129. 

3  Following  a  suggestion  of  Williamson,  the  symbols  for  oxygen,  carbon, 
sulphur  were  barred  in  Kekul^'s  formulae  to  indicate  that  the  combining  weights 
were  double  those  of  the  equivalent  notation. 


MIXED  TYPES  49 

Oxamic  acid  may,  in  the  same  way,  be  referred  to  a  mixed  water  and 
ammonia  type  : 

H)  H) 

H  N  H  IN 

H  e  ««,{ 

H/€  H/€ 

Kekule's  Theory  of  Atomicity.  Kekule  at  once  saw,  as  William- 
son had  previously  done  (p.  47),  that  such  a  fusion  of  types  to  a 
condensed  or  mixed  type  can  only  occur  where  a  polybasic  or 
polyatomic  radical  is  present  in  the  place  of  two  or  three  atoms  of 
hydrogen.  Using  the  dashes  of  Odling  to  indicate  atomicity  and 
the  double  atoms,  which  Williamson  had  revived  to  distinguish 
Gerhardt's  atomic  weights  (C  =  12,  O  =  16)  from  Gmelin's  equivalents 
(C  =  6,  O  =  8),  Kekule  defines  the  radicals  as  follows: 

*A  monatomic  radical  can,  therefore,  never  hold  together  two 
molecules  of  the  types.' 

*  A  diatomic  radical  can  unite  two  molecules  of  the  types,'  e.  g. 

He  <&) 


Thionyl  chloride.       Sulphuric  acid.  Urea, 

or,  can  replace  two  hydrogen  atoms  of  the  type,  e.  g. 


Sulphuric  anhydride.  Cyanic  acid. 

'A  triatomic  radical  can  unite  in  the  same  way  three  molecules  of 
the  types;'  e.  g. 

P8 


Phosphoric  acid.  Glycerine.  Trichlorhydrin. 

or  it  can  also  replace  three  atoms  of  hydrogen  in  two  molecules  of 
water,  e.  g. 

P6)  A 
H/6* 

Metaphosphoric  acid. 

Perhaps  the  most  important  part  of  this  remarkable  and  suggestive 
memoir  is  the  reference  to  the  basicity,  i.  e.  valency  of  the  individual 
elements. 

PT.  i  E 


50  ORGANIC  CHEMISTRY 

Growth  of  the  Theory  of  Valency.  As  the  whole  foundation  of 
modern  structural  chemistry  may  be  said  to  rest  upon  the  theory 
of  valency,  it  is  necessary  to  trace  carefully  the  line  of  thought  which 
culminated  in  its  development. 

It  is  just  possible  that  had  no  previous  literature  existed  on  the 
subject,  this  property  of  the  elements  would  have  disclosed  itself  to 
Kekule's  penetrating  intellect.  It  is  none  the  less  true  that  the 
merit  of  having  been  the  first  to  offer  a  clear  exposition  of  the  subject 
belongs  to  Frankland. 

In  studying  the  organo-metallic  compounds,  to  which  reference 
has  been  made  (p.  37),  Frankland  was  struck  with  the  fact  that  there 
appears  to  be  a  definite  saturation  capacity  for  the  metals,  and  that  the 
number  of  radicals  present  affects  the  number  of  inorganic  elements 
which  attach  themselves  to  the  metal  in  a  symmetrical  fashion.  It 
was  this  fact  which  led  him  to  oppose  Kolbe's  view  that  the  radicals 
are  conjugated  with  the  metal.  At  the  close  of  this  paper l  Frank- 
land  expressed  himself  as  follows :  '  When  the  formulae  of  inorganic 
chemical  compounds  are  considered,  even  a  superficial  observer  is 
struck  with  the  general  symmetry  of  their  construction ;  the  com- 
pounds of  nitrogen,  phosphorus,  antimony,  and  arsenic  especially 
exhibit  the  tendency  of  these  elements  to  form  compounds  con- 
taining three  or  five  equivalents  of  other  elements,  and  it  is  in  these 
proportions  that  their  affinities  are  best  satisfied  ;  thus  in  the  ternal 
group  we  have  N03,  NH3,  NI3,  NS3,  P03,  PH3,  PC13,  Sb03,  SbH3, 
SbCl3,  AsO3,  AsH3,  AsCl3,  &c. ;  and  in  the  five-atom  group  N05, 
NH4O,  NH4I,  P05,  PH4I,  &c.  Without  offering  any  hypothesis 
regarding  the  cause  of  this  symmetrical  grouping  of  atoms,  it 
is  sufficiently  evident,  from  the  examples  just  given,  that  such 
a  tendency  or  law  prevails,  and  that  no  matter  what  the  character  of 
the  uniting  atoms  may  be,  the  combining  power  of  the  attracting  element, 
if  I  may  be  allowed  the  term,  is  always  satisfied  by  the  same  number 
of  these  atoms.' 

Two  years  later,  in  his  first  publication  of  theoretical  importance, 
Note  on  a  New  Series  of  Organic  Acids  containing  Sulphur?  Kekule 
refers  to  the  basicity  of  the  elements.  Various  organic  compounds 
of  the  water  type  such  as  alcohol,  ether,  acetic  acid,  and  acetic 
anhydride  were  heated  with  the  sulphides  of  phosphorus  and  the 
typical  oxygen  replaced  by  sulphur.  He  shows  that  the  new  typical 
formulae  of  Gerhardt  are  well  adapted  for  expressing  these  changes. 
If,  according  to  the  equivalent  notation,  phosphorus  chloride  breaks 

1  Phil  Trans.,  1852,  417.  «  Annalen,  1854,  90,  309. 


GROWTH  OF  THE  THEORY  OF  VALENCY     51 

up  alcohol  into  C4H5C1  +  HC1,  why  should  not  phosphorus  sulphide 
produce  two  compounds  C4H5S  +  HS  instead  of  their  remaining 
united  as  mercaptan?  With  Gerhardt's  notation  the  change  is 


manifest,  °2^  1  0  becomes  °2^  1  S,  but  with  phosphorus  chloride 

C  H  Cl 
the  alcohol  divides  up  thus,     VrVn  •     He  writes  :  *  It  is  not  merely 

II  Li 

a  difference  of  notation,  but  it  is  an  actual  fact  that  one  atom  of 
water  contains  two  atoms  of  hydrogen  and  only  one  atom  of  oxygen  ; 
and  that  for  one  indivisible  atom  of  oxygen  the  equivalent  of  chlorine 
is  divisible  by  two  ;  whereas  sulphur,  like  oxygen,  is  dibasic,  one  atom 
being  equivalent  to  two  of  chlorine.' 

In  the  memoir  already  referred  to  (p.  48),  On  tJie  so-called  Conju- 
gated Compounds  and  the  Theory  of  Polyatomic  Radicals,1  Kekule's 
views  on  atomicity  take  a  clearer  and  more  definite  shape.  He  says  : 
'  The  molecules  of  chemical  compounds  are  formed  by  the  union  of 
atoms.  The  number  of  atoms  of  other  elements  which  are  attached 
to  one  atom  of  an  element,  or  (if  in  the  case  of  compound  bodies  one 
prefers  not  to  extend  the  idea  to  elements)  of  a  radical,  is  dependent 
on  the  basicity  or  affinity  of  the  constituents/ 

'  The  elements  fall  into  three  main  groups  : 

'  (1)  Monobasic  or  monatomic,  e.  g.  H,  Cl,  Br,  K  ;  (2)  dibasic  or 
diatomic,  e.  g.  O,  S  ;  (3)  tribasic  or  triatomic,  e.  g.  N,  P,  As.  From 
these  are  derived  the  chief  types,  HH,  OH2,  NH3,  and  the  secondary 
types,  HC1,  SH2,  PH3.'  In  a  footnote  on  p.  133  he  adds  that  carbon 
is  tetrabasic  or  tetratomic. 

After  this  defence  of  Gerhardt's  formulae  and  clear  exposition 
of  atomic  structure,  it  is  curious  to  find  Kekule  reverting  to  the 
equivalent  notation  in  his  very  next  memoir  on  the  constitution 
of  fulminating  mercury;  but  such  is  the  despotic  power  of  long 
established  custom. 

In  discussing  the  constitution  of  fulminating  mercury,  Kekule2 
pointed  out  its  analogy  with  a  series  of  compounds  which  might  be 
considered  as  belonging  to  the  same  type  as  marsh  gas,  using  the 
word  in  Dumas'  sense  of  one  compound  being  related  to  another  by 
substitution.  He  succeeded,  in  fact,  in  liberating  the  cyanogen  as 
cyanogen  chloride  by  chlorination,  and  converting  fulminating  mer- 
cury into  chloropicrin. 

Methyl  chloride,  chloroform,  chloropicrin,  and  acetonitrile  were 

1  Annalen,  1857,  104,  133.  2  Annalen,  1857,  101,  200. 

£  2 


52 


ORGANIC  CHEMISTRY 


grouped  with  marsh  gas,  and  written  in  the  equivalent  notation 
thus: 

Marsh  gas 
Methyl  chloride 
Chloroform 
Chloropicrin 
Acetonitrile 
Fulminating  mercury 
Thus  Kekul6  introduced  a  new  type,  that  of  marsh  gas,  and  with  its 
introduction  the  fixity  of  Gerhardt's  types  was  dissolved  ;  for  it  now 
became  evident  that  the  grouping  of  the  elements  depended,  not  on 
the  nature  of  the  type,  but  upon  that  of  the  elements  themselves. 
As  typical  formulae  were  not  intended  to  represent  the  position  of 
the  atoms,  it  became  a  matter  of  choice  to  which  type  a  compound 
belonged.     Thus,  methyl  ether  may  be  equally  well  derived  from 
the  water  or  the  marsh  gas  type : 


H 

H 

H 

H 

H 

H 

H 

Cl 

H 

Cl 

Cl 

Cl 

(NOJ 

Cl 

Cl 

Cl 

H 

H 

H 

(C2N) 

(N04) 

Hg 

Hg 

(C2N) 

CH3 
CH3 


or 


H 
H 
H 

O 

H 
H 
H 


C 


c 


Methylamine  in  the  same  way  may  be  referred  to  ammonia,  marsh 
gas,  or  hydrogen : 


H 
H 
H 
H 


H 

H 

HJ 


I    CH3) 
I    NHJ 


Quadrivalence  of  Carbon.  Early  in  1858  Kekule's  celebrated 
paper  appeared  in  Liebig's  Annalen  on  The  Constitution  and  Meta- 
morphoses of  Chemical  Compounds,  and  on  the  Chemical  Nature  of 
Carbon,  in  which  are  embodied  his  views  on  the  valency  of  carbon 
and  the  linking  of  carbon  atoms.1  Shortly  afterwards  an  equally 
remarkable  memoir  on  the  same  subject  by  A.  S.  Couper2  was 
published  independently  in  the  Annales  under  the  title  of  A  new 
C/iemical  Theory. 

Keknle*'s  Theory.     Kekule  has  told,  in  a  very  graphic  way,  how 
these  new  ideas  arose.     It  was  during  his  stay  in  London. 

*  One  fine  summer  evening  I  was  returning  by  the  last  omnibus 

1  Annalen,  1858, 106,  129;  Ostwald's  Elassiker,  No.  145. 
8  Ann.  Chim.  Phys.,  1858  (3),  53,  469. 


KEKULfrS  THEORY  53 

"  outside  "  as  usual,  through  the  deserted  streets  of  the  metropolis, 
which  are  at  other  times  so  full  of  life.  I  fell  into  a  reverie,  and  lo  ! 
the  atoms  were  gambolling  before  my  eyes  !  Whenever,  hitherto, 
these  diminutive  beings  had  appeared  to  me  they  had  always  been  in 
motion  ;  but  up  to  that  time  I  had  never  been  able  to  discern  the 
nature  of  their  motion.  Now,  however,  I  saw  how,  frequently,  two 
smaller  atoms  united  to  form  a  pair  ;  how  a  larger  one  embraced  two 
smaller  ones  ;  how  still  larger  ones  kept  hold  of  three  or  even  four 
of  the  smaller  ;  whilst  the  whole  kept  whirling  in  a  giddy  dance. 
I  saw  how  the  larger  ones  formed  a  chain,  dragging  the  smaller  ones 
after  them,  but  only  at  the  ends  of  the  chain.  .  .  .  This  was  the 
origin  of  the  Stmcturtheorie.'1 

'If  we  consider,'  writes  Kekule  in  his  memoir,  'the  simplest 
compounds  of  carbon,  CH4,  CH3C1,  CC14,  CHC13,  COC12,  C02,  CS2, 
CHN,  it  is  very  striking  that  the  amount  of  carbon  which  chemists- 
recognize  as  the  atom,  that  is,'  the  smallest  part,  always  unites  with 
four  atoms  of  a  monatomic  or  two  of  a  diatomic  element,  that  gene- 
rally the  sum  of  the  chemical  units  which  are  bound  to  an  atom  of 
carbon  is  equal  to  four.  This  leads  to  the  view  that  carbon  is  tetr- 
atomic.' 

*  For  substances  which  contain  several  atoms  of  carbon,  one  must 
suppose  that  a  portion  of  the  atoms  at  least  is  held  by  the  attraction 
of  the  carbon,  and  that  the  carbon  atoms  themselves  are  united  to 
one  another,  whereby  naturally  a  part  of  the  attraction  of  the  one  is 
neutralized  by  an  equal  attraction  on  the  part  of  the  other.' 

'The  simplest  and  consequently  most  probable  case  of  such  a 
union  of  two  carbon  atoms  is  that  one  unit  of  affinity  of  one  carbon 
atom  is  bound  to  one  of  the  other.  Of  these  2x4  units  of  affinity 
of  the  two  carbon  atoms,  two  will  be  used  to  unite  the  two  carbon 
atoms,  and  six  will  remain  over  to  attach  the  other  elements.  In 
other  words  the  group  C2  is  hexatomic.  .  .  .' 

'If  more  than  two  carbon  atoms  unite  in  the  same  way,  the 
basicity  of  the  carbon  group  will  be  increased  by  two  units  for  each 
additional  carbon  atom.  Thus  the  number  of  hydrogen  atoms  which 
may  be  combined  with  n  carbon  atoms  is  expressed  by 


'  .  .  .  Up  to  this  point  we  have  assumed  that  all  the  atoms  attaching 
themselves  to  carbon  are  held  by  the  affinity  of  the  carbon.  It  is 
equally  conceivable,  however,  that  in  the  case  of  polyatomic  elements 
(0,  N,  &c.)  only  a  part  of  the  affinity  —  for  example,  only  one  of  the 
1  The  Kekule  Memorial  Lecture,  by  F.  R.  Japp,  Trans.  Ctem.  Soc.,  1898,  73,  97. 


54  ORGANIC  CHEMISTRY 

two  units  of  affinity  of  the  oxygen,  or  only  one  of  the  three  units  of 
the  nitrogen  —  is  attached  to  carbon  ;  so  that  one  of  the  two  units  of 
affinity  of  the  oxygen  and  two  of  the  three  units  of  affinity  of  the 
nitrogen  remain  over  and  may  be  united  with  other  elements. 
These  other  elements  are  therefore  only  in  indirect  union  with  the 
carbon,  a  fact  which  is  indicated  by  the  typical  mode  of  writing  the 
formulae.* 

Kekule  does  not  recognize  only  this  one  kind  of  attachment  of  the 
carbons.  He  points  out  that  another  kind  of  combination  may  occur 
involving  a  closer  union  of  the  carbon  atoms,  an  idea  which  was 
expanded  seven  years  later  (1865)  in  his  theory  of  the  benzene  ring. 

Conper's  Theory.  Couper1  arrived  at  similar  conclusions  from 
a  different  starting-point.  His  paper,  which  is  characterized  by 
remarkable  perspicuity  and  breadth  of  view,  has  perhaps  scarcely 
received  the  full  recognition  which  it  merits.  Couper  begins  by 
rejecting  the  type  theory  of  Gerhard  t  as  artificial  and  unphilosophical, 
and  lays  stress  on  the  fact  that  the  properties  of  compounds  must  in 
the  end  depend  on  the  nature  of  their  atoms.  Gerhardt's  system  is 
like  referring  a  language  to  certain  types  of  words,  from  which  all 
others  are  formed,  instead  of  to  the  individual  letters.  The  atoms, 
he  considers,  are  held  together  by  virtue  of  two  properties,  elective 
affinity  or  chemical  affinity  and  degree  of  affinity,  which  corresponds 
exactly  to  our  word  valency. 

In  regard  to  carbon  (1)  it  unites  with  an  even  number  of  hydrogen 
atoms,  and  (2)  it  unites  with  itself.  The  maximum  number  of  atoms 
with  which  it  can  combine  is  four.  The  following  are  some  of  the 
formulae  proposed  by  Couper  which,  apart  from  the  presence  of  the 
double  atom  of  oxygen,  bear  a  complete  resemblance  to  those  in 
modern  use  (C  =  12  ;  O  =  8)  : 


{S 


OH 


CH3  CH3  CH3  H3C 

Ethyl  alcohol.  Acetic  acid.  Ethyl  ether. 

r  (  0-OH 

? 


H 
V  1  0-OH 


Tartaric  acid. 
1  Nature,  1909,  p.  329. 


COUPER'S  THEORY  55 

The  two  papers  by  Kekule  and  Couper  are  the  foundations  upon 
which  the  modern  structural  formulae  of  organic  compounds  rest. 
It  must  not  be  supposed  that  the  typical  formulae  were  at  once  dis- 
carded in  favour  of  the  modern  notation.  On  the  contrary,  the 
typical  notation  was  in  general  use  for  many  years  after  the  above 
memoirs  had  appeared,  and  was  even  retained  in  Kekule's  textbook 
of  organic  chemistry  which  was  published  as  late  as  1866.  It  is 
evident,  from  the  facts  recorded  in  the  next  chapter  having  reference 
to  the  basicity  of  lactic  acid,  that  the  true  significance  of  Kekule's 
and  Couper's  views  had  not  then  (1863)  taken  root. 

Modern  Structural  Formulae.  It  is  in  fact  difficult  to  assign 
any  particular  date  to  the  introduction  of  the  modern  structural  nota- 
tion. Its  adoption  was  the  result  of  a  gradual  and  almost  imper- 
ceptible development.  Frankland  made  a  distinct  advance  by  deriving 
his  compounds  from  the  marsh  gas  or  its  condensed  type,  and  break- 
ing up  the  rest  of  the  molecule  attached  to  the  typical  carbon  atoms 
into  tervalent  groups  thus  : 

rH3  (H.  (0 

OH 


2]H  "IOH  ^10 

(OH  (OH 

Alcohol.  Acetic  acid.  Oxalic  acid. 

Although  there  is  evidence  that  the  principle  of  carbon  linkages,  like 
that  suggested  by  Couper,  was  fully  recognized  before  its  actual 
adoption,1  it  was  not  until  1866  that  the  first  appearance  of  the 
modern  system  of  notation  occurs  in  two  papers  by  Erlenmeyer,8 
followed  in  1867  by  a  clear  exposition  of  the  subject  by  Frankland.3 
The  necessity  for  the  replacement  of  rational  by  structural  formulae' 
became  more  and  more  emphasized  with  the  growth  of  the  subject, 
and  especially  with  the  extension  of  the  views  on  isomerism  which 
demanded  a  more  delicate  and  perfect  language  for  its  expression. 

REFERENCES. 

History  of  Chemistry,  by  A.  Ladenburg,  trans,  by  L.  Dobbin.  Clay,  Edinburgh, 
1905. 

History  of  Chemistry,  by  E.  von  Meyer,  trans,  by  G.  McGowan.  Macmillan. 
London,  1898. 

Rise  and  Development  of  Organic  Cliemistry,  by  C.  Schorlemmer,  edited  by 
A.  Smithells.  Macmillan,  London,  1894. 

Treatise  on  Chemistry,  Vol.  Ill,  Pt.  i,  Introduction,  by  Roscoe  and  Schorlemmer. 
Macmillan,  London,  1881. 

Chemical  Society  Memorial  Lectures,  1893-1900.     Gurney  &  Jackson,  London. 

1  Kekule's  Lehrbuch  der  organ.  Clum.,  vol.  i,  pp.  164  and  174. 

9  Jnnafcn,  1866,  137,  351 ;  130,  211.  »  Annalen,  1867;  142,  1. 


CHAPTER  II 
THE  VALENCY  OF  CARBON 

THE  early  history  of  valency  has  been  described  in  the  introduc- 
tory chapter  (p.  50).  Whilst  its  later  development,  especially  in 
connection  with  organic  chemistry,  has  been  attended  by  results  of 
the  highest  theoretical  and  practical  value,  the  subject  as  a  whole 
has  made  little  advance.  This  is  due  to  the  apparently  variable 
character  of  the  property  in  every  element  including  carbon,  and  is 
plainly  indicated  by  the  number  of  more  or  less  unsatisfactory 
attempts  to  find  a  comprehensive  generalisation. 

The  term  valency  is  applied  to  the  saturation  capacity  of  one  element 
for  other  elements,  and  must  not  be  confused  with  the  strength  of  the 
attachment  or  chemical  affinity ;  it  is  in  fact  noteworthy  that  the 
lowest  valency  is  found  among  those  elements  in  the  two  end 
groups  of  the  periodic  system  which  exhibit  the  greatest  affinity,  or, 
as  Hinrichsen l  puts  it,  '  the  energy  content  of  an  atom  is  the  greater 
the  smaller  its  active  valency.' 

The  various  speculations  on  the  relation  existing  between  valency 
and  affinity  and  the  origin  of  the  phenomena  will  be  discussed 
presently. 

As  hydrogen  is  one  of  the  elements  of  lowest  combining  capacity 
which  rarely  unites  with  more  than  one  atom  of  a  second  element,  it 
might  serve  as  a  useful  standard  for  determining  the  valency  of  the 
other  elements ;  but  the  small  number  of  hydrides  which  it  forms, 
especially  with  the  metallic  elements,  rather  restricts  its  application. 
The  halogens  which  might  be  employed  in  place  of  hydrogen  cannot 
always  be  relied  on,  as  they  do  not  possess  a  constant  valency  and 
form  compounds  such  as  H2F2,  KI3  and  a  whole  series  of  oxides. 
Another  method  which  might  be  employed  is  to  divide  the  atomic 
weight  by  the  equivalent  of  the  element  as  determined  by  electrolysis 

1  Annalen,  1904,  366,  168. 


VALENCY,  A  VARIABLE  QUANTITY  57 

or  by  the  composition  of  the  oxide.  According  to  Faraday's  law  the 
same  quantity  of  electricity  passed  through  an  electrolyte  liberates 
equivalent  weights  of  the  different  elements,  or,  in  other  words, 
equivalent  weights  of  different  elements  convey  the  same  quantity  of 
electricity.  But  in  this  case  it  is  found  that  a  metal  in  different 
states  of  combination,  such  as  iron  in  ferrous  and  ferric  salts,  exhibits 
different  valencies,  the  first  liberating  28  and  the  second  18*6  parts 
of  iron  compared  with  one  of  hydrogen.  The  use  of  the  oxide  presents 
difficulties  of  another  kind,  for  the  equivalent  in  the  oase  of  Pb3O4 
would  give  a  valency  value  for  lead  determined  by  the  fraction 
207/77-6. 

Returning  to  the  first  method,  how  are  we  to  interpret  the  valency 
of  nitrogen  in  the  two  compounds,  ammonia  NH3  and  azoimide  N3H  ? 
Here  a  very  simple  explanation  suffices.  In  both  compounds  the 
nitrogen  is  tervalent,  but  in  the  second  the  nitrogen  atoms  are  linked 
together  in  the  form  of  a  univalent  group  : 

N 


This  formulates  the  mutual  attachment  of  similar  multivalent  atoms 
and  introduces  an  entirely  new  conception  into  the  idea  of  valency. 
It  was  a  fundamental  part  of  Kekule's  and  Couper's  theory  of  the 
structure  of  carbon  compounds,  and  has  become  so  interwoven  with 
the  idea  of  valency  that  its  intrinsic  novelty  is  apt  to  be  overlooked. 
All-important  as  the  conception  has  turned  out  in  its  application  to 
the  compounds  of  carbon,  which  stands  almost  alone  as  an  element 
of  definite  valency,  it  has  afforded  the  widest  interpretation  in 
deterir'ning  the  structure  of  the  compounds  of  most  of  the  other 
elements. 

Thus,  in  the  case  of  alumina,  A1203,  we  may  formulate  a  structure 
in  which  two  atoms  of  metal  or  of  oxygen,  or  the  three  atoms  of 
oxygen,  or,  again,  an  alternate  atom  of  aluminium  and  oxygen  are 
directly  attached,  so  that  any  arrangement  may  be  devised  to  suit  the 
desired  valency  of  the  atoms  under  consideration.  In  short,  whilst 
the  linking  of  atoms  has  afforded  a  firm  foundation  for  building  up 
the  structure  of  compounds  with  elements  of  definite  valency,  its 
employment  in  other  cases  has  generally  served  to  increase  the 
number  of  possible  formulae. 

Valency,  a  Variable  Quantity.  Influenced  by  the  success  which 
attended  the  application  to  carbon  of  the  principle  of  linkages,  Kekule 
was  led  to  infer  that  valency  was  a  definite  and  unalterable  quantity 


58  THE  VALENCY  OF  CARBON 

bound  up  with  each  atom.  The  variable  valency  of  certain  elements, 
especially  of  the  nitrogen  and  halogen  groups  of  the  periodic  system, 
subsequently  led  to  the  complete  abandonment  of  this  view.  It 
was  impossible,  for  example,  to  reconcile  the  structure  of  NH4C1  as 
consisting  of  NH3  in  molecular  attachment  to  HC1  with  Meyer  and 
Lecco's  observation  that  diethylmethylamine  +  methyl  iodide  gave 
the  same  product  as  dimethylethylamiiie  +  ethyl  iodide  and  also 
with  the  existence  of  the  numerous  optically  active  ammonium 
compounds  (Part  II,  p.  304). 

If,  with  Kolbe,  we  regard  each  element  as  possessing  a  maximum 
valency,  a  view  which  has  been  widely  adopted,  the  question  arises 
as  to  how  this  maximum  value  may  be  ascertained,  for  it  is  a  curious 
fact  that  in  the  periodic  table  the  oxygen  value  rises  from  group  I  to 
group  VII,  whilst  the  hydrogen  value  rises  to  group  IV  and  then  falls 
again.  If  we  adopt  the  valency  of  the  highest  oxide  we  are  con- 
fronted with  the  uncertain  value  for  oxygen,  which  sometimes  appears 
to  function  as  a  quadrivalent  atom.  On  the  other  hand,  the  atomic 
weight  being  known,  the  periodic  classification  or  the  atomic  number 
(see  p.  97,  footnote)  affords  at  times  a  valuable  guide. 

Abegg  and  Bodlander1  regard  each  atom  as  possessing  the  same 
total  number  of  valencies,  namely  eight,  which  are  distributed 
between  positive  and  negative,  the  positive  diminishing  from  7  to  1 
in  the  first  seven  groups  of  the  periodic  system  and  the  negative 
increasing  in  the  same  order.  Of  these  two  kinds  the  positive  or 
negative  predominates  in  each  atom  and  is  termed  the  normal  valency, 
whilst  the  subordinate  kind  is  called  a  contravalency.  In  the  middle 
or  fourth  group,  which  includes  carbon,  neither  predominates,  and 
this  is  supposed  to  explain  the  stability  of  carbon  in  its  union  with 
both  electropositive  and  electronegative  elements,  as  in  methane  and 
carbon  tetrafluoride.  The  distribution  of  normal  and  contra-valencies 
in  the  seven  groups  is  as  follows : 

normal  +142  +  3  -3-2-1 

±4 
contra    -7-6-5  +5  +  6  +  7 

The  weak  point  of  the  scheme  is  the  existence  of  the  seven  contra- 
valencies  among  the  alkali  metals,  for  which  at  present  there  appears 
to  be  no  evidence. 

According  to  Clayton,2  this  decrease  in  the  valency  of  an  element 
for  hydrogen  in  the  more  electronegative  groups  cannot  be  due  to 

1  Zeit.  anorg.  Chem.,  1899,  20,  453  ;  1904,  39,  330. 
*  Trans.  Chem.  Soc.,'  1916,  109,  1046. 


TERVALENT  CARBON 


59 


decrease  of  affinity,  and  must  therefore  have  relation  to  some  other 
factor  which  increases  by  a  constant  quantity  from  group  to  group. 
If  this  is  so,  the  difference  should  be  capable  of  being  detected  by 
reference  to  the  actual  hydroxyl  derivatives  of  these  elements  or  their 
dehydrated  forms. 

Thus,  taking  the  series  containing  four  hydrogen  atoms  having  the 
maximum  valency  of  their  fully  hydrated  forms,  the  elements  in 
groups  V  to  VIII  will  be  represented  as  follows : 


Group. 

V. 

VI. 

VII. 

VIII. 

Hydrated  form 

EH4OH 
-H20 

EH4(OH\ 
-2H30 

EH4(OH)3 
-3HaO 

EH4(OH)4 
-4H2O 

Dehydrated  form 

EHS 

EHa 

EH 

No  hydrids 

e.g. 

NH3 

OH3 

C1H 

Clayton  distinguishes  between  the  primary  valency  which  reaches 
a  maximum  of  4  and  a  secondary  valency  which  is  determined  by  the 
number  of  hydroxyl  groups.  If  one  each  of  the  primary  and  secondary 
valencies  unite  or  neutralize  one  another,  the  effective  valency  will 
be  lowered  by  two.  For  example,  if  the  secondary  valency  in  group  V, 
which  binds  the  hydroxyl,  unites  with  one  of  the  primary  valencies 
which  attaches  the  hydrogen,  the  total  valency  will  be  lowered  by  two 
and  NH3  will  result.  In  group  VI,  H2O,  and  in  group  VII,  C1H 
will  be  formed,  whilst  the  elements  in  group  VIII  do  not  combine 
with  hydrogen. 

Clayton  indicates  the  primary  and  secondary  valencies  by  a  con- 
tinuous and  a  dotted  line  respectively,  which,  when  unattached,  are 
represented  as  forming  a  loop. 

Ammonium  hydroxide  and  ammonia  and  methyl  ether  and  its 
additive  compound  with  hydrogen  chloride  are  represented  by  the 
following  formulae  : 


H    OH 

I/ 
H— N— H 


H— NC 
H 


Cl    II 

\/ 

CH,— O— CIL 


H3C— O— CH. 


Tervalent  Carbon.  Although  the  valency  of  carbon  has  offered 
fewer  anomalies  than  that  of  any  other  element  in  the  interpretation 
of  the  structure  of  its  numerous  compounds,  there  exists  one  example, 
namely,  triphenylmethyl  C(CGH5)3  in  which  there  is  reason  to  believe 
that  carbon,  at  least  in  solution,  is  tervalent.  There  is  intrinsically 
nothing  novel  or  surprising  in  the  existence  of  a  combined  atom  with 
one  unused  valency,  for  nitrogen  in  nitric  oxide,  NO,  must  possess 
a  free  valency  whether  oxygen  is  bi-  or  quadrivalent.  It  may  be 


60  THE  VALENCY  OF  CARBON 

pointed  out  that  in  both  compounds  the  unsaturated  element  is 
attached  to  an  electronegative  group  or  atom.  Triphenylmethyl 
contains  the  strongly  electronegative  group  (C6H5)3  united  to  carbon, 
whereas  in  nitric  oxide  the  nitrogen  is  linked  to  electronegative 
oxygen.  Such  compounds  as  CH3,  NH2,  or  NH4  in  which  the  carbon 
and  nitrogen  are  combined  with  electropositive  elements  are  unknown. 
These  and  similar  facts  have  led  Michael l  to  draw  the  conclusion  that 
union  with  negative  atoms  can  produce  self-saturation,  but  not  if 
the  combination  includes  positive  ones.  The  tendency  for  carbon 
and  nitrogen  to  polymerise  (that  is,  for  similar  atoms  to  unite)  is 
promoted  by  union  with  1,  2,  or  3  atoms  of  hydrogen.  Thus  CH, 
CH2,  and  CH3  appear,  not  as  free  entities,  but  as  acetylene,  ethylene, 
and  ethane,  and  NH2  as  hydrazine. 

Werner,2  who  views  valency  as  a  quantity  which  may  be  differently 
distributed  according  to  the  nature  of  the  atoms  or  groups  involved  (see 
p.  85),  considers  that  the  phenyl  groups  in  fcriphenylmeihyl  saturate 
more  of  the  carbon  affinity  than,  say,  hydrogen  atoms,  leaving  less 
affinity  for  further  union.  The  compound  is,  in  short,  more  saturated 
than  methyl. 

Triphenylmethyl.3  In  1900  Gomberg,4  in  attempting  to  prepare 
hexaphenylethane  (C0H6)3C .  C(C6H5)3  by  the  action  of  finely  divided 
silver  on  triphenylmethyl  chloride  (bromide  or  iodide)  in  benzene 
solution,  obtained  a  colourless,  crystalline  compound  having  the  com- 
position of  the  required  hydrocarbon,  but  possessing  very  unusual 
properties.  Though  colourless  in  the  solid  form,  it  dissolves  in  most 
organic  solvents  with  a  distinct  orange  yellow  colour.  It  is  apparently 
unsaturated,  for  it  combines  greedily  with  free  oxygen  to  form  a  per- 
oxide (C6H5)3CO .  CO(C0H5)3,  with  the  halogens  to  form  triphenyl- 
methyl halide,  with  hydrogen,  in  presence  of  finely  divided  platinum,  to 
form  triphenyl  methane,  with  nitric  oxide  and  nitrogen  dioxide  to  form 
the  nitroso  compound  with  the  first,  and  a  mixture  of  nitro  compound 
and  nitrous  ester  with  the  second.5 

(C6H5)3C .  NO,  (C6H5)3C .  N02 ,  (C,H5)3C .  ONO 

Nitroso  Nitro  Triphenylmethyl 

triphenylmethyl.  triphenylmethyl.  nitrite. 

1  J.  prakt.  Chem.,  1899,  60,  295. 

2  Neuere  Anschauungen  avf  dem  Gebiete  der  anorganischen  Chemie,  p.  79. 

3  For  a  more  detailed  account  of  the  subject  the  following  should  be  con- 
sulted :  Gomberg,  J.  Amer.  Chem.  Soc.,  1914,  36,  1144,   and  Das  Triphenylmethyl  by 
J.  Schmidlin,  Chemie  in  Einzeldarstellung,  vol.  vi,  Enke,  Stuttgart,  1914. 

*  Ber.,  1900,  33,  3150. 

6  Schlenk  and  Mair,  Ber.t  1911,  44.  1169.  . 


TRIPHENYLMETHYL  01 

It  also  forms  an  additive  compound  with  quinone,1 

/OC(C6H6)3 


CCH4 


NOC(C6H5)3 

Moreover,  it  unites  with  a  variety  of  organic  solvents,  paraffins, 
olefines,  and  aromatic  hydrocarbons,  ethers,  aldehydes,  ketones,  esters, 
and  nitriles,  and  with  carbon  disulphide  and  chloroform,  in  all  of 
which  two  molecules  of  triphenyl  methyl  are  combined  with  one 
molecule  of  the  organic  solvent  in  the  form  of  well-defined  crystalline 
substances,  which  are,  however,  easily  dissociated  on  heating.  It  also 
enters  into  reactions  with  phenol,2  primary  and  secondary  amines, 
phenylhydrazine 3  and  diazomethane.4  Dissolved  in  ether  out  of  con- 
tact with  oxygen  it  combines  with  metallic  sodium.5  The  sodium 
compound  NaC(C6H5)3  reacts  normally  with  alkyl  halides.  forming 
alkyltriphenylmethanes,  and  undergoes  condensation  with  ketones 
and  esters  very  much  after  the  manner  of  the  Grignard  reagent6 
(p.  208). 

Since  Gomberg  first  obtained  triphenylmethyl,  a  large  number  of  simi- 
lar compounds  containing  a  variety  of  aryl  radicals  have  been  prepared, 
and  they  all  possess  the  same  striking  characteristics.  They  combine 
readily  with  free  oxygen,  &c.,  and  though  with  few  exceptions  colour- 
less in  the  solid  state,  yield  a  variety  of  coloured  solutions  when  dis- 
solved.7 The  difficulty  encountered  in  determining  the  true  structure 
of  these  substances  arises  from  the  fact  that  whereas  some  of  these 
compounds,  such  as  tribiphenylmethyl  (C6H5C6H4)3C  prepared  by 
Schlenk  and  his  co-workers,8  are  unimolecular  in  solution  (deter- 
mined by  the  cryoscopic  method),  others,  for  example,  triphenyl- 
methyl, are  mainly  bimolecular.9  It  would,  therefore,  appear  that 
in  addition  to  the  solid,  colourless  compound  there  are  two  coloured 
substances,  a  bi-  and  unimolecular  compound  existing  in  the  dissolved 
state.  But  Schmidlin  has  shown  that  in  a  solution  of  triphenyl- 
methyl, the  colourless  and  yellow  modification  exist  side  by  side,10 
forming  an  equilibrium  mixture  which  varies  with  the  solvent  and 
the  temperature.  For  the  freshly  dissolved  substance,  which  is  at  first 

Schmidlin,  Ber.,  1910,  43,  1298.  2  Schmidlin,  Ber.,  1912,  45,  3180. 

Schlenk  and  Bornhardt,  Ber.,  1911,  44,  1175. 
Schlenk  and  Bornhardt,  Annakn,  1912,  394,  183. 
Schlenk  and  Marcus,  Ber.,  1914,  47,  1664. 
Schlenk  and  Ochs,  Ber.,  1916,  49,  608. 
Schmidlin.  Ber.,  1912,  45,  3171,  3183. 

Schlenk,  VVeickel,   and  Herzenstein,  Annalen,   1910,  372,   1  ;    Schenk  and 
Rerinig,  Annalen,  1912,  394,  180. 

9  Gomberg,  Ber.,  1904,  37,  2049.  10  Ber.,  1908,  41,  2471. 


62  THE  VALENCY  OF  CARBON 

colourless,  becomes  quickly  yellow.  On  shaking  the  solution  in  con- 
tact with  air  it  loses  its  colour  owing  to  the  formation  of  the  insoluble 
peroxide,  when  the  yellow  colour  rapidly  reappears  as  a  fresh  quantity 
of  the  colourless  compound  passes  into  the  coloured  modification.  It 
therefore  follows  that  the  colourless  and  coloured  compounds  undergo 
isomeric  change,  but  that  the  coloured  modification  is  the  more  re- 
active of  the  two.  Schmidlin  has  further  shown  that  the  coloured 
substance  is  in  all  cases  unimolecular,  and,  though  the  quantity  in 
triphenylmethyl  is  small,  there  is  sufficient  present  (5  per  cent,  in 
benzene,  17  per  cent,  in  naphthalene)  to  impart  a  yellow  colour  to 
the  liquid. 

What  then  is  the  relation  between  the  colourless  bimolecular  com- 
pound and  the  coloured  unimolecular  compound  ? 

The  question  has  been  answered  by  comparing  the  properties  of 
triphenylmethyl  and  triphenylmethyl  chloride.  Both  substances  are 
colourless  in  the  crystalline  state,  and  triphenylmethyl  chloride  also 
yields  colourless  solutions ;  but  both  dissolve  in  liquid  sulphur  di- 
oxide with  a  yellow  colour,  and  both  exhibit  a  fafrly  high  conduc- 
tivity. They  therefore  offer  a  close  analogy.  It  is  frequently  found 
that  isomerisation  from  a  colourless  to  a  coloured  substance  is 
accompanied  by  a  change  from  a  benzenoid  to  a  quinoid  structure,  and 
this  has  been  shown  to  occur  in  the  case  of  jp-bromotriphenylmethyl 
chloride.  Though  silver  chloride  has  no  action  on  the  substance  when 
dissolved  in  benzene,  in  sulphur  dioxide  solution  the  bromine  atom 
is  replaced  by  chlorine,  and  on  evaporating  the  solvent  colourless 
jp-chlorotriphenylmethyl  chloride  is  obtained.1  The  change  is 
readily  explained  on  the  assumption  of  an  intermediate  half-quinoid 
or  quinol  form  first  proposed  by  Kehrmann  for  the  coloured  salts  of 
triphenylmethyl 2 


(C6H5)2C  : 


The  quinoid  halogens  thus  become  labile,  and  an  interchange  of  the 
chlorine  of  the  silver  chloride  for  bromine  occurs,  which  on  removal 
of  the  solvent  passes  into  ^J-chlorotriphenylmethyl  chloride. 


.    ^_=\C1 
Cl 

1  Gomberg,  1909,  42,  406. 

2  Ber.,  1901,  34,  3815 ;  see  also,  Colour  and  Structure,  this  volume,  Part  II. 


TRIPHENYLMETHYL  63 

Again,  by  simply  dissolving  ^-bromotriphenylmethyl  chloride  in 
sulphur  dioxide  and  removing  the  solvent  a  mixture  of  jp-bromo- 
triphenylchloride  and  jp-chlorotriphenylbromide  is  produced  : 

/Br 


|(C6H5)2CClCcH4Br 
t(CcH5)2CBrC6H4Cl 

In  this  way  triphenylmethyl  chloride  in  isomerising  to  the  yellow 
modification  passes  into  the  quinol  form,  and  at  the  same  time  under- 
goes ionization  into  a  basic  ion, 


•  %  Quinocarbonium  ion. 

to  which  Gomberg  has  given  the  name  quinocarbonium,  and  an  acid 
ion.    The  coloured  salts  are  termed  quinocarbonium  salts. 

The  existence  of  hydroxytriphenylcarbinol  in  a  yellow  and  colour- 
less modification,  melting  respectively  at  139-140°  and  157-159°, 
which  are  interconvertible  (acids  and  the  action  of  light  produce  the 
quinoid,  whilst  alkalis  promote  the  benzenoid  form),  points  to  the 
same  explanation.1 


(C6H5)2C/ 


C6H4OH  /=\    /OH 

-^    (CCH;)2C:/ 
OH  \=/\OH 


Benzenoid  Quinoid 

m.  p.  157-159.  m.  p.  139-140. 

What,  then,  is  the  nature  of  the  yellow  ionized  compound  present 
in  the  sulphur  dioxide  solution  of  triphenylmethyl  ?  By  analogy  it 
should  consist  of  the  basic  quinocarbonium  ion  and  an  acid  ion,  which 
may  be  the  tervalent  radical, 


\/ 


ii 


(C0H;).2C:<  ><      +  C(CliH5)3 


\ 

On  the  assumption  that  dilution  does  not  change  the  equilibrium  be- 
tween two  dynamic  isomers,  whereas  ionization  is  known  to  do  so, 

1  Gomberg,  J.  Amer.  Chem  Soc.,  1913,  35,  1035. 


64  THE  VALENCY  OF  CARBON 

Piccard  l  determined  the  effect  of  dilution  on  the  intensity  of  the 
colour  of  triphenylmethyl,  and  showed  that  it  does  not  follow  Beer's 
law,2  but  that  the  colour  is  intensified  ;  in  view  of  recent  observations 
on  the  effect  of  solvents  on  the  equilibria  of  dynamic  isomers,3 
Piccard's  conclusion  that  ionization  occurs  cannot  be  sustained. 
Nevertheless,  the  observation  is  of  interest. 

The  existence  of  the  corresponding  unionized  compound  of  the 
formula, 


C(C6H6)3 
Jacobson's  formula. 

which  was  first  suggested  by  Jacobson,  is  supported  by  observations 
of  Gomberg  and  Cone.4  Following  the  same  line  of  reasoning  which 
determined  the  quinol  formula  for  the  coloured  modification  of  the 
unimolecular  compound,  these  observers  prepared  p-bromotriphenyl- 
methyl  chloride,  which,  acted  upon  by  molecular  silver,  removed  not 
only  two  atoms  of  chlorine  giving  the  triaryl  compound,  but  also  one 
atom  of  bromine.  This  could  only  occur  if  the  nuclear  bromine 
atom  became  attached,  as  in  the  former  case,  to  the  quinoid  nucleus 
(indicated  by  an  asterisk). 

_  T>r* 

(C.EW.C:/       "V 

^  -  /N-C(C6H5)2C0H4Br 


Moreover,  Jacobson's  formula  explains  in  a  simple  way  the  action  of 
acids  on  triphenylmethyl,5  which  yields  a  compound  first  obtained  by 
Ullman  and  Borsum.6 


"    "" 


(CCH5)2C:  -*  (ccH5)2CH 


The  only  other  compound  whose  structure  has  yet  to  be  considered 

1  Annalen,  1911,  331,  34. 

2  According  to  Beer's  Law  the  intensity  of  colour  in  a  solution  is  proportional 
to  its  concentration. 

3  Hantzsch,  Ber.,  1910,  43,  3049  ;  1911,  44,  1772  ;  K.  H.  Meyer,  Annalen,  1911, 
380,  212. 

4  Ber.,  1906,  ?9,  3174  ;  1907,  40,  1830. 

5  Gomberg,  Ber.,  1902,  35,  3918  ;  1903,  38,  376. 

6  Ber.,  1902,  35,  2877;  Jacobson,  Ber.,  1905,  38,  196. 


TRIPHENYLMETHYL  65 

is  the  colourless  bimolecular  modification  which  exists  in  the 
free  state  and  in  solution  in  equilibrium  with  the  coloured  mono- 
molecular  compound.  It  seems  probable  that  it  is  either  hexaphenyl- 
ethane  or  an  aggregate  of  two  molecules  of  the  tervalent  radical. 

The  synthesis  of  hexaphenylethane  would  have  settled  the  question, 
but  so  far  all  attempts  to  prepare  it  have  failed.  On  the  other  hand 
both  tetra-  and  pentaphenylethane  have  been  obtained  by  Gomberg  and 
Cone,  who  describe  them  as  stable  substances  exhibiting,  at  least  at 
ordinary  temperatures,  no  tendency  to  absorb  oxygen,  or  otherwise 
to  behave  as  unsaturated  compounds. 

In  conclusion,  it  would  seem  that  every  property  of  the  triaryl- 
methyl  compounds  may  be  explained  by  the  existence  of  four  modifica- 
tions which  in  solution  are  in  equilibrium.  This  equilibrium  is  re- 
presented by  Gomberg 1  as  follows :. 

(C6H5)3C 

U 

/ 

(C6H5)2C:/  (C6H5)2C: 

C(C6H5) 

Whether  or  not  hexaphenylethane  exists,  or  the  coloured  unimole- 
cular  compound  possesses  the  quinol  structure,  it  is  abundantly  proved 
that  the  bimolecular  compound  readily  dissociates  in  solution,  break- 
ing up  into  two  molecules  of  the  triarylmethyl  compound  in  which 
carbon  is  tervalent. 

Schlenk2  has  also  observed  that  the  compound  obtained  by  the 
action  of  sodium  on  aromatic  ketones  has  the  formula  (Ar)2C .  ONa 
and  not  the  double  formula  (see  p.  247),  and  the  compound,  for- 
merly regarded  as  ditolane  hexachloride,  appears  from  recent  deter- 
minations also  to  have  half  the  molecular  weight,  and  is  therefore 
tolane  trichloride  C6H5CC12 .  CC1C6H5 ,3  Both  compounds  therefore 
contain  tervalent  carbon. 

Wieland,4  it  may  be  added,  has  found  that  tetraphenyl  hydrazine 
breaks  up  on  heating  into  diphenyl  nitride  (C6H5)2N  containing 
bivalent  nitrogen. 

Bivalent  Carbon.  There  are  a  number  of  compounds  in  which 
there  is  reason  to  believe  that  bivalent  carbon  is  present.  Among 

1  Bcr.,  1913,  46,  228. 

*  Bw.,  1911,  44,  1182;  1913,  46,  2840. 

*  Lob.,  Ber.,  1903,  36,  3063.         *  Annahn,  1911,  381,  200, 

FT.  I  F 


66          THE  VALENCY  OF  CARBON 

these  are  carbon  monoxide,  CO  ;  fulminic  acid,  C  :NOH  ;  and,  according 
to  Nef,  the  alkyl  and  acyl  isocyanides,  RN  :  C,  and  acetylene  and  its 
halogen  derivatives.  Although  it  is  possible  to  interpret  the  structure 
of  all  these  compounds,  except  the  last,  as  containing  mutually  saturated 
valencies  by  making  oxygen  quadrivalent  or  nitrogen  quinquevalent, 
there  are  chemical  as  well  as  stereochemical  considerations  which  make 
such  a  supposition  improbable.  If  we  accept  the  usual  stereochemical 
arrangement  of  the  carbon  bonds,  it  is  difficult  to  conceive  of  these 
four  linkages  being  brought  simultaneously  into  action  with  any 
other  single  atom.  The  chemical  properties  of  most  of  these  com- 
pounds point  in  the  same  direction. 

Structure  of  the  Isocyanides.  Supposing  the  inability  of  bi- 
valent carbon  in  carbon  monoxide  to  form  additive  compounds  (except 
with  chlorine  and  caustic  soda)  to  be  due  to  the  presence  of  electro- 
negative oxygen,  then  the  replacement  of  oxygen  by  a  more  electro- 
positive group  might  restore  its  additive  power.  Such  was  Nef  s 
reasoning.1  He  selected  for  his  inquiry  alkyl  and  acyl  isocyanides 
R  .  N  :  C  and  found  that  his  anticipations  were  correct.  The  alkyl  and 
acyl  isocyanides  form  the  following  series  of  additive  compounds  : 

1.  With  the  halogens  (Cl,  Br,  I)  combination  takes  place  vigorously 
at  low  temperatures.     The  reaction,  according  to  Nef,  proceeds  in. 
steps.     The  halogen  molecule  X2  unites  first  by  virtue  of  its  residual 
valency  and  then  separates  into  its  constituent  atoms. 

X  X 

RN:C<+X:X  -»   RN:C/||    ->   RN  :  C/' 
||  \X  \X 

That  the  halogens  actually  take  up  these  positions  is  proved  by  the 
fact  that  union  with  amines  yields  guanidines. 

2.  With  acid  chlorides  (acetyl,  benzoyl,  carbonyl,  and  chloroformic 
ester)  the   following  are  formed,  in  which  the  halogen  may  be 
replaced  by  hydroxyl  : 

RN  :  CC1 

/Cl  ,Cl  ,Cl 

:C<  ,RN:C<  ,  CO,    RN  :  C< 

XCOCH3  XCOC6H5  \COOC2H5 

RN  :  CC1 


RN 


8.  The  isocyanides  unite  with  free  oxygen,  reduce  metallic  oxides, 
and  combine  directly  with  sulphur  to  form  carbimides  and  thiocar- 
bimides  : 

RN  :  C  :  0,  RN  :  C  :  S 

1  J.  Amtr.  Chem.  Soc.,  1904,  26,  1549;  Annakn,  1892,  270,  267;  1894,  230,  291. 


STRUCTURE   OF  THE   ISOCYANIDES  67 

4.  They  combine  with   amines   H  —  NHR    and    hydroxylamine 
H—  NHOH  : 


/ 
C< 
NHR  \NHOH 

5.  They  combine  with  alcohols,  mercaptans,  and  hydrogen  sulphide: 


, 

RN:C  ,  RN:C< 

\ 


/ 
RN:C<  ,          RN:C<  ,         RN  :  C< 

\OC2H5  NsCjH5  \3H 

6.  With  phenyl  magnesium  bromide  a  compound  of  the  formula, 


<vy6iA5 
MgBr 
is  formed. 

7.  In  absence  of  water  the  halogen  acids  produce  additive  com- 
pounds which  by  analogy  are  represented  as  follows : 

JRNiC/     )HC1 
\  M3K, 

Moreover,  like  other  unsaturated  compounds  they  polymerise ;  thus 
phenylisocyanide  rapidly  changes  to  a  resinous  mass.  Hydrolysis, 
on  the  other  hand,  produces  the  formamide  RNH  .  CHO,  from  which 
it  appears  that  carbon  in  the  isocyanide  had  three  available  bonds  ;  but 
the  exact  mechanism  of  the  addition  process  is  unknown,  and  it  is 
quite  conceivable  that  the  elements  of  water  first  attach  themselves 
to  the  carbon  atom  and  that  this  is  followed  by  the  migration  of 
hydrogen  to  nitrogen. 

-»  RNH.  CHO 
X)H 

Nef  further  points  out  that  many  of  the  above  reactions  are  reversible 
and  the  isocyanide  and  its  addendum  may  dissociate  at  an  appropriate 
temperature  in  the  same  manner  as  ammonium  chloride. 

There  seems  no  reason,  therefore,  to  doubt  the  existence  of  bi- 
valent carbon  in  alkyl  and  acyl  isocyanides. 

Structure  of  the  Metallic  Cyanides.  The  metallic  cyanides 
probably  possess  a  similar  structure.  Like  the  alkyl  and  acyl  iso- 
cyanides, alkaline  cyanides  readily  unite  with  oxygen.  Potassium 
cyanide  forms  potassium  cyanate  on  oxidation  and  probably  unites 
with  chlorine  to  form  KNCC1.2.  Like  the  alkyl  isocyanides  the 
alkaline  cyanides  form  double  salts  with  the  heavy  metallic  cyanides, 
whereas  the  few  double  salts  of  the  alkyl  cyanides  are  much  less 

F2 


68  THE  VALENCY  OF  CARBON 

stable.1  A  significant  fact  is  the  existence  of  sodium  ferrofulminate 
Na4Fe(ON :  C)6  +  18H2O,  which  has  been  proved  to  contain  bivalent 
carbon,  so  that  sodium  ferrocyanide  by  analogy  should  be  written 
Na4Fe(N:C)6.2  Another  fact  discovered  by  Nef  also  points  in  the 
same  direction.  Potassium  cyanide  and  ethyl  hypochlorite  give 
ethyl  cyanimido  carbonate,  the  formation  of  which  can  only  be 
satisfactorily  explained  by  adopting  the  isocyanide  structure. 


/>C2H5 
-»  KNC<  -*    KNC.OC2H5 


KNC 

____  \C1  KCN 

C1C  :  NK 

X)C2H5 

-»    HNC<  +  KOH  +  KC1 

H20  \CN 

The  behaviour  of  silver,  mercury,  and  certain  other  metallic  cyanides 
of  the  heavy  metals  differs  from  that  of  the  alkaline  cyanides.  They 
are  not  oxidised  by  permanganate  and  yield  isocyanides  with  the 
alkyl  halides,  whereas  the  alkaline  cyanides  yield  cyanates  in  the  first 
case  and  mainly  cyanides  in  the  second.  On  the  other  hand,  the 
acyl  halides,  such  as  acetyl  chloride,  give  cyanides  and  not  iso- 
cyanides with  silver  cyanide.  The  last  fact  disposes  of  the  view  that 
the  two  classes  of  metallic  cyanides  are  differently  constituted,  the 
alkaline  cyanides  being  normal  and  the  silver  and  mercury  com- 
pounds having  an  '  iso  '  structure.  How  are  these  observations  to 
be  reconciled  ?  Nef  considers  that  both  classes  of  metallic  cyanides 
have  the  iso  structure  and  that  the  difference  in  behaviour  lies  in 
the  electrochemical  character  of  the  metal.  Whilst  the  alkaline 
cyanides  react  with  the  alkyl  halides  by  direct  addition  to  give  the 
alkyl  cyanide  thus  : 

,K 
KNC+RI-»KNC<^      -»    NCR  +  KI 

silver  cyanide  reacts  by  direct  substitution  : 


There  seems  to  be  also  some  evidence  that  potassium  cyanide  forms 
additive  compounds  with  alkyl  iodides. 

Wade  3  in  a  subsequent  investigation,  whilst  accepting  Nef  *s  views 
as  to  the  structure  of  the  metallic  cyanides,  has  given  a  rather 
different  interpretation  to  the  interaction  of  silver  cyanide  with  the 
alkyl  halide,  which  he  represents  as  follows  : 

1  Hofmann  and  Bugge,  JSer.,  1907,  40,  1772  ;  Ramberg,  Ber.,  1907,  40,  2578. 
*  Annahn,  1894,  280,  335.  »  Trans.  Chtm.  Soc.,  1902,  91,  1603. 


STRUCTURE   OF  THE   METALLIC  CYANIDES          69 
AgNC  +  RI  -*   AgNC  -»  RNC  +  AgI 

A 

Thus,  while  addition  to  the  alkaline  cyanide  with  its  strongly 
electropositive  metal  takes  place  at  the  carbon  atom,  in  the  case  of 
silver  cyanide  with  the  weaker  electropositive  metal  it  occurs  at  the 
nitrogen  atom.  It  must  he  admitted  that  neither  proof  appears 
very  conclusive. 

Sidgwick1  has  made  the  ingenious  suggestion  that  in  all  cases 
addition  to  carbon  takes  place,  and  that  the  additive  compound  may 
exist  in  two  stereoisomeric  forms : 

RCI  RCI 


MN  NM        M  =  Metal 

I.  II. 

Formula  II,  corresponding  to  the  synaldoximes,  represents  the  additive 
compound  of  the  alkaline  cyanide  and  yields,  by  removal  of  the 
metallic  iodide,  the  alkyl  cyanide  as  formulated  by  Nef.  The  first 
formula  (I),  which  represents  the  additive  compound  with  silver 
cyanide,  undergoes  the  Beckmann  conversion,  and  by  interchange  of 
metal  and  alkyl  group,  followed  by  the  detachment  of  the  metallic 
iodide,  yields  the  isocyanide. 

RCI  MCI  C 

II    -"  II     -*>  II 

MN  RN  RN 

But  there  is  no  proof  whatever  of  any  such  reaction. 

The  Structure  of  Hydrogen  Cyanide.  The  study  of  the  structure 
of  hydrogen  cyanide,  which,  like  the  nitiiles  and  isocyanides,  may 
exist  in  two  different  forms,  has  produced  evidence  of  such  a  con- 
flicting character  that  it  seems  at  present  purposeless  to  offer  more 
than  a  brief  outline  of  the  arguments  for  and  against  the  one  or 
other  structure  until  the  subject  has  advanced  a  stage.  It  is  clear 
that  no  purely  chemical  method  will  suffice  to  settle  the  question, 
for  reasons  already  given  in  the  chapter  on  isomeric  change  (Part  II, 
p.  313).  The  following  facts  have  been  advanced  in  favour  of  the 
nitrile  structure.  Hydrogen  cyanide  undergoes  hydrolysis  by  alkalis 
which  are  without  action  on  alkyl  isocyanides,  whereas  acids  which 
act  slowly  on  hydrogen  cyanide  decompose  isocyanides  with  great 
rapidity.  Again,  the  alkyl  isocyanides,  like  the  alkali  cyanides,  which 
may  be  assumed  to  be  iso  compounds,  dissolve  silver  cyanide,  whilst 

1  Proc.  Ctew,  Soc.t  1905,  21,  120. 


70  THE  VALENCY   OF  CARBON 

nitriles  and  hydrogen  cyanide  do  not.  When  hydrogen  cyanide  is 
heated  it  polymerises;  but  there  is  no  evidence  that  it  undergoes 
isomeric  change ;  nitriles,  on  the  other  hand,  yield  isocyanides.  The 
polymeride  obtained  from  hydrogen  cyanide  forms  glycosine  on 
hydrolysis  and  is  therefore  aminomalonitrile,  NH2.CH(CN)2,  indicat- 
ing thereby  that  the  nitrile  rather  than  the  isocyanide  has  undergone 
polymerisation.1  There  are  a  large  number  of  chemical  facts  which 
point  in  the  same  direction,  such  as  the  preparation  of  hydrogen 
cyanide  from  formamide 2  and  formoxime 3  by  dehydration,  a  reaction 
which  corresponds  to  nitrile  formation.  Its  additive  compounds  with 
metallic  chlorides4  resemble  those  of  the  nitriles  and  its  stability 
towards  ethylhypochlorite  and  chlorine  is  in  marked  contrast  to  the 
alkyl  isocyanides5  (p. 66).  Its  union  with  diazomethane  to  form 
acetonitrile 6  has  been  discounted  as  a  fact  in  favour  of  the  nitrile 
structure  since  the  discovery  that  isocyanide  is  also  formed.7 

Many  of  the  physical  constants  also  indicate  a  nitrile  structure  ; 
its  refractivity,8  its  high  dielectric  constant  and  ionising  power 
correspond  to  those  of  the  lower  nitriles.9  Michael  and  Hibbert 10  take 
the  same  view  and  regard  the  true  hypothetical  acid  as  having  the 
isocyanide  structure,  but  from  the  absence  of  salt  formation  when 
pure  hydrogen  cyanide  is  added  to  trialkylamines  (though  the 
cyanides  of  these  substances  can  be  formed  in  other  ways)  they 
conclude  that  the  actual  compound  is  formonitrile.  It  is  true  that 
the  primary  and  secondary  amines  do  yield  unstable  salts,  but  it  is 
contended  that  the  union  is  accompanied  by  isomeric  change,  a  form 
of  argument  which  has  an  air  of  special  pleading. 

On  the  other  hand  Chattaway  and  Wadmore  n  adopt  the  isocyanide 
formula  on  account  of  the  ease  with  which  hydrogen  is  exchanged 
for  halogen  in  hydrogen  cyanide  and  its  salts. 

C  :  NH,  C  :  NCI,  C :  NK 

Cyanogen  chloride  has  the  characteristic  properties  of  a  nitrogen 
chloride   and   consequently  the   isocyanide    formula   for  hydrogen 
cyanide  explains  most  satisfactorily  its  whole  chemical  behaviour. 
The  weak  character  of  the  free  acid  compared  with  the  effect  of 

1  Lescoeur  and  Rigaufc,  Compt.  rend.,  1879,  89,  310. 

2  Hofmann,  Trans.  Chem.  Soc.,  1863,  16,  74. 

s  Dunstan  and  Bossi,  Trans.  Chem.  Soc.,  1898,  73,  360. 

4  Klein,  Annalen,  1850,  74,  86. 

5  Nef,  Annalen,  1895,  287,  274. 

c  von  Pechmann,  Ber.,  1895,  28,  857. 

7  Peratoner  and  Palazzo,  AM  R.  Accad.  Lincei,  1907, 16.  432. 

8  Bruhl,  Zeit.physik.  Chem.,  1895,  16,  512. 

9  Schlundt,  Zeit.  phijsik.  Chem.,  1901,  5,  157. 

10  Annalen,  1909,  364,  64.  n  Trans.  Chem.  Soc.,  1902,  81,  192. 


THE   STRUCTURE   OF  HYDROGEN  CYANIDE          71 

the  cyanogen  group  in  increasing  the  acidity  of  acetic  acid  (a  fact 
which  has  been  advanced  by  Ostwald  as  indicating  an  isocyanide 
structure), 

Acetic  acid,  K  =  0-0018 
Cyanacetic  acid,  K  =  0-3700 

loses  its  force  when  a  similar  comparison  is  drawn  between  the 
CC13  group  in  chloroform  and  the  same  group  in  trichloracetic  acid, 
the  former  producing  a  neutral  non-electrolyte  and  the  latter  a  strong 
acid  with  an  affinity  constant,  K  =  120-0.  Nef  has  attributed  the 
poisonous  character  and  low  boiling-point  of  hydrogen  cyanide  to 
the  isocyanide  structure  ;  but  it  appears  now  that  alkyl  cyanides  as 
well  as  cyanogen  produce  symptoms  resembling  hydrogen  cyanide 
poisoning.  In  its  ready  formation  of  additive  compounds,  such  as 
HCN  .  HC1  and  2HCN  .  3HC1,  it  appears  to  resemble  the  isocyanides  ; 
but,  from  their  behaviour,  it  seems  that  the  probable  formulae  are  : 


, 

C1C<          ,  HC<  HC1 

\H  \NH.CHC12 

The  weight  of  evidence  appears  therefore  in  favour  of  the  nitrile 
structure  ;  but,  as  stated  above,  chemical  reactions  alone  are  incapable 
of  settling  the  question. 

The  Structure  of  Fulminic  Acid.  The  presence  of  bivalent 
carbon  in  fulminic  acid  has  been  demonstrated  by  Nef.1  Mercury 
fulminate,  which  was  discovered  by  Howard  in  1800  and  has  since 
found  such  an  extended  application  as  a  detonator,  is  prepared  by  the 
action  of  mercuric  nitrate  in  nitric  acid  on  ethyl  alcohol.  The  analysis 
corresponds  to  the  molecular  formula  HgC2N202,  and  it  is  therefore 
isomeric  with  mercury  cyanatc.  Passing  over  the  earlier  researches 
of  Kekule  (p.  51),  who  regarded  it  as  a  derivative  of  nitro- 
acetonitrile,  it  has  been  shown  that  hydrochloric  acid  breaks  it  up 
into  hydroxylamine  and  formic  acid,  suggesting  the  following  formula 
for  the  acid  : 

C:NOH 

<J:NOH 

The  single  carbon  formula  C  :  NOH  or  carbyloxime  has  been  deduced 
from  its  synthesis.  Nef  obtained  it  by  the  action  of  mercuric  chloride 
on  sodium  nitro  methane,  which  probably  reacts  by  forming  a  mercuric 
salt  of  nitromethane  and  then  loses  the  elements  of  water. 

1  Anwlen,  1894,  280,  275,  303. 


72  THE  VALENCY   OF   CARBON 

H2C  :  NOhg  =  C :  NOhg  +  H2O  hg  =  ^ 

O 

Moreover,  mercury  fulminate  when  acted  on  by  nitrous  acid  is 
converted  into  methyl  nitrolic  acid,  (NO  JHC :  NOH.  Seeing  that  both 
nitromethane  and  methyl  nitrolic  acid  contain  only  one  carbon  atom, 
there  is  strong  proof  of  the  presence  of  a  single  carbon  atom  in 
fulminic  acid.  The  formation  of  methyl  nitrolic  acid  from  a  ful- 
minate and  nitrous  acid  as  well  as  of  formylchloride  oxime,  by  the 
action  on  the  sodium  salt  of  the  former  with  hydrochloric  acid,  and 
the  existence  of  an  additive  compound  of  hydrogen  chloride  and 
silver  fulminate,  all  point  to  the  presence  of  bivalent  carbon. 

TT  TT  TT 

HON  :  C/  HON  :  C/  AgON  :  C/ 

\N02  \C1  \C1 

Additive  compounds  with  hydrogen  sulphide  and  sulphate  are  also 
known  and  are  readily  prepared. 

TT  TT 

HON  :  C/  HON  : 


:C\, 


\SH  \OS03H 

The  structure  of  formylchloride  oxime  is  further  determined  by  its 
decomposition,  on  standing,  into  hydroxylamine  hydrochloride  and 
carbon  monoxide,  and  by  its  conversion  with  aniline  into  phenyl 
isouretin,  the  structure  of  which  has  been  fully  established. 

M 

HO.NHCC 

XNC6H5 

It  may  also  be  added  that  silver  nitrite  converts  formyl  chloride 
quantitatively  into  silver  fulminate. 

/Cl 

2AgN02  =  AgON  :  C  +  AgCl  +  HN03 


HC/      + 
^0 


In  addition  to  Nefs  synthesis,  already  mentioned,  fulminic  acid 
has  been  obtained  by  Wieland l  from  methyl  nitrolic  acid  and  similar 
compounds,  the  formation  of  which  is  easily  accounted  for  in  each 
case  by  adopting  Nefs  formula.  Scholl 2  found  that  in  presence  of 
benzene  and  a  mixture  of  anhydrous  and  hydrated  aluminium  chloride, 
mercury  fulminate  may  be  converted  into  benzaldoxime.  The  reaction 
is  most  simply  explained  in  the  following  way.  The  hydrated  alu- 

»  Ahrens'  Vortrage,  1909,  14,  385. 

8  Ber.t  1899,  32,  3492 ;  1903,  36,  10,  322,  648. 


THE   STRUCTURE   OF  FULMINIC   ACID  73 

minium  chloride  liberates  hydrogen  chloride  from  the  fulminic  acid 
and  unites  with  it  to  form  formylchloride  oxime,  which  then  combines 
with  benzene. 

/H  5;          /H 

HON  :  C<      +  CCH6  =  HON  :  C<          +  HC1 
XC1  \06H5 

Finally,  the  molecular  weight  of  the  sodium  salt  has  been  ascer- 
tained by  the  cryoscopic  method,  whilst  the  molecular  conductivity 
shows  that  the  acid  is  monobasic,  and  both  point  to  the  acid  possessing 
the  unimolecular  formula,  C  :  NOH.  All  that  remains  is  to  briefly 
indicate  the  formation  of  fulminic  acid  from  lffe£gft^hich  probably 
passes  through  the  following  series  of  changes  : 
CH3  .  CH2OH  ->  CH3CHO  ->  HON  :  CH  .  CHO  ->  HON  :  CH  .  COOH 

->  HON  :C(N02).  COOH  ->  HONiCHCNOJ  -»  HON:C 
The  acid  then  unites  with  mercury  to  form  mercury  fulminate. 

Structure  of  Acetylene  Compounds.  Nef  l  found  that  if  dibrom- 
ethylene,  C2H2Br2,  is  acted  upon  with  aqueous-alcoholic  soda  it  yields 
a  gas,  bromacetylene,  02HBr.  This  substance  is  exceedingly  reactive; 
it  combines  vigorously  with  oxygen,  phosphoresces,  gives  the  ozone 
reaction,  smells  like  hydrogen  cyanide,  and  is  poisonous.  The  alkyl 
and  acyl  derivatives  of  acetylene,  on  the  other  hand,  have  a  sweet 
smell  and  other  properties  in  marked  contrast  to  the  above  bromine 
compound.  Dibromacetylene,  C2Br2,  is  obtained  by  the  action  of 
alcoholic  potash  in  the  cold  on  tribromethylene.  It  smells  like  an 
isocyanide,  and  is  both  very  poisonous  and  spontaneously  inflam- 
mable. Moreover,  it  combines  directly  with  sodium  ethoxide  and 
phenoxidetoform  dibromophenyl'-  and  ethyl-  vinyl  ethers,  C2Br2H  .  OR, 
and  with  hydriodic  acid  to  form  dibromoiodethylene,  C2HBr2I.  The 
fact  that  all  three  compounds  give  dibromacetic  acid  or  its  ester  on 
oxidation,  taken  in  conjunction  with  the  unstable  character  of  dibrom- 
acetylene,  its  poisonous  properties  and  striking  similarity  in  smell 
to  the  isocyanides,  led  Nef  to  regard  both  mono-  and  dibromacetylene 
as  derivatives  of  acetylidene,  CH2:C<,  CHBr:C<,  CBr2:C<.  For 
similar  reasons,  and  also  because  diiodacetylene  breaks  up  on  oxida- 
tion into  tetraiodethylene  and  carbon  monoxide,  the  former  is 
regarded  as  diiodacetylidene. 


The  metallic  compounds  are  formulated  in  a  similar  fashion, 
CaC:  C<(,  Ag2C  :  C{,  &c.,  and  acetylene  itself  is  represented  as  possessing 
the  acetylidene  structure. 

1  Annalen,  1897,  298,  332  ;  1899,  308,  325. 


74  THE   VALENCY   OF  CARBON 

Although  exception  may  be  taken  to  Nefs  views  on  the  structure 
of  the  acetylene  compounds,  the  existence  of  bivalent  carbon  in  the 
other  groups,  which  have  been  discussed,  seems  to  be  firmly  estab- 
lished. The  question  whether  the  unsaturated  valencies  should  be 
represented  as  mutually  saturating  one  another,  or  free,  or,  as  Nef 
supposes,  an  equilibrium  mixture  of  both,  the  free  being  the  reactive, 
and  the  combined  the  inactive  form,  does  not  seem  to  possess  much 
real  significance. 

RR.C~|     ;r±    RR.C< 

Inactive.  Reactive. 

The  Nature  of  Unsaturated  Groups.  By  an  unsaturated  group, 
as  distinguished  from  an  unsaturated  atom,  we  wish  to  imply  the 
union  of  two  atoms  whose  affinities  are  not  saturated.  When  the 
union  lies  between  carbon  and  carbon  we  obtain  the  unsaturated 
hydrocarbons  and  their  derivatives.  It  is  clear  that  in  a  case  of  this 
character,  as,  for  example,  in  ethylene  and  acetylene,  we  may  indicate 
unsaturation  in  several  ways.  Adopting  Werner's  view  that  valency 
may  distribute  itself  unequally  over  the  atom,  a  larger  amount  will 
be  available  for  uniting  unsaturated  than  for  saturated  carbon,  or 
unsaturation  may  be  indicated  by  the  union  of  bivalent  or  tervalent 
carbon  atoms,  leaving  a  certain  amount  of  affinity  free,  or,  again,  the 
unsaturated  valencies  may  be  represented  by  the  method  adopted  by 
Nef  in  bivalent  carbon  compounds,  as  saturating  one  another.  In 
the  last  case  we  obtain  what  are  known  as  double  or  treble  bonds  or 
linkages.  Although  the  double  and  treble  bond  is  very  generally 
accepted,  it  may  be  well  to  state  briefly  the  evidence  upon  which  it 
rests.  We  will  then  proceed  to  discuss  the  theory  of  free  valencies, 
i.  e.  the  union  of  bivalent  and  tervalent  carbon,  and  finally  Werner's 
theory  in  its  application  to  unsaturated  compounds. 

Theory  of  the  Double  Bond.  In  the  first  place,  there  is  nothing 
intrinsically  improbable  in  the  notion  of  a  force  of  attraction  being 
concentrated  at  definite  points  on  the  atom  or  having  a  definite 
direction,  which  may  be  symbolized  by  bonds.  The  view,  indeed, 
receives  substantial  support  from  the  theory  of  the  valency  electron, 
which  is  discussed  later  (p.  96).  This  theory  represents  valency  as 
residing  in  one  or  more  electrons  which  occupy  a  definite  position  in 
or  near  the  surface  of  the  positively  charged  atom  and  send  out  lines 
of  force  which  either  terminate  on  other  atoms  and  so  bind  them  or 
curve  back  on  the  atom  from  which  they  proceed. 

But  there  are  other  grounds  upon  which  the  theory  of  the  double 
bond  rests.  All  unsaturated  compounds  unite  with  an  even  number 


THEORY  OF  THE  DOUBLE  BOND        75 

of  univalent  atoms  or  groups;  in  other  words,  the  saturation  of  one 
imsaturated  carbon  atom  necessitates  that  of  the  other,  and  moreover 
the  unsaturated  carbon  atoms  invariably  adjoin  one  another.  There 
is  an  obvious  connection  of  a  special  kind  between  the  two  un- 
saturated carbon  atoms,  for  which  the  device  of  the  double  bond  is 
made  to  serve. 

If  ethylene  and  ethane  differed  merely  in  the  number  of  hydrogen 
atoms  attached  to  the  two  carbon  atoms,  we  should  expect  the  heats 
of  combustion  and  formation  and  other  physical  constants  to  be 
determined  solely  by  the  presence  or  absence  of  hydrogen  ;  but  we 
know  that  this  is  not  the  case.   The  physical  constants  for  unsaturated 
compounds  are  fully  discussed  in  a  subsequent  chapter  (Part  II, 
chap,  i),  but  it   may  be  stated   here  that  the  difference  between 
saturated   and   unsaturated   carbon  is  clearly  brought   out   in  the 
values  for  molecular  solution-volume,  refractivity,  magnetic  rotation, 
and  heat  of  combustion.     For  example,  the  heats  of  combustion  of 
ethane,  ethylene,  and  hydrogen  given  by  Thomsen  are : 
C2HG         37044     mol.-grm.-cals. 
C2H4        333-35 
H2          68-36 

If  the  value  for  ethylene  were  that  of  ethane  less  two  atoms  of 
hydrogen,  it  would  be  37044  —  68-36  =  302-08,  whereas  much  more 
heat  is  evolved.  The  conclusion  is  that  unsaturated  carbon  atoms 
are  more  easily  severed  than  the  saturated  atoms,  and  less  energy  is 
consequently  absorbed  in  the  process  of  cleavage. 

Unsaturated  carbon  possesses  therefore  a  higher  energy  content  or 
the  carbon  atoms  are  at  a  higher  chemical  potential  than  when 
saturated.  But  evidence  of  a  more  convincing  kind  is  derived  from 
stereochemical  considerations. 

Evidence  of  Stereochemistry.  The  principles  of  stereochemistry, 
enunciated  by  van  't  Hoff  (Part  II,  chap,  iii),  are  based  upon  the 
relation  subsisting  between  optical  activity  and  the  presence  of 
asymmetric  carbon  in  saturated  compounds,  and  again  on  well- 
marked  physical  and  chemical  differences  among  the  so-called 
geometrical  isomers  of  the  olefine  series.  This  theory  rests  upon 
the  assumption  of  a  definite  position  and  direction  of  the  valency 
attachments.  But  it  offers  something  more  than  an  explanation  of 
these  forms  of  isomerism,  important  though  they  are. 

We  must  be  careful  to  recognize  clearly  that  the  method  of  indi- 
cating unsaturation  by  a  double  bond  is  not  taken  to  imply  a  firmer 
connection  between  the  unsaturated  carbon  atoms  any  more  than  an 


76  THE  VALENCY   OF  CARBON 

increased  valency  value  indicates  additional  strength  of  affinity 
(p.56).1  The  double  bond  is,  in  short,  a  point  of  weakness  in  a 
molecule  rather  than  of  strength.  Thus,  on  oxidation  with  perman- 
ganate or  fusion  with  potash,  the  double  link  forms  the  point  of 
cleavage  and,  as  already  pointed  out,  the  heat  of  combustion  of  an 
unsaturated  compound,  atom  for  atom,  is  greater  than  that  of  a 
saturated  compound.  It  contains  a  larger  store  of  available  energy 
and  is  consequently  less  stable. 

Various  theories  giving  prominence  to  the  idea  of  the  weakness  of 
the  double  bond  have  been  advanced,  and  rest  mainly  on  the  space 
arrangement  of  the  carbon  bonds.  If  we  suppose  the  bonds  to 
diverge  at  equal  angles  (109-5°)  from  the  central  carbon  atom  and  to 
retain  their  positions  when  the  two  carbon  atoms  become  doubly 
linked,  the  space  arrangement  viewed  in  perspective  will  appear  as 
shown  in  Fig.  1. 

A 
B 


Fia.  1. 

If  the  single  bond  represents  the  direction  and  measure  of  the  force 
of  affinity,  the  resultant  of  the  two  forces  acting  at  an  angle  of  109-5° 
will  not  be  the  equivalent  of  the  same  forces  acting  in  a  straight  line 
but  very  much  less.  According  to  Baeyer's  strain  theory  (see  p.  178), 
if  the  result  of  the  double  linking  tends  to  bend  the  two  pairs  of 
bonds  from  their  original  positions  into  a  straight  line  joining  the  two 
carbon  atoms,  a  condition  of  strain  will  be  set  up  which  will  occasion 
instability.  This  theory  is  developed  more  fully  in  connection  with 
the  formation  of  cyclic  compounds  (p.  178)  ;  but  it  may  be  mentioned 
here  as  a  significant  fact  that  the  ring  systems  which  occasion  least 
deformation  in  the  normal  arrangement  of  the  bonds  contain  five  and 
six  atoms,  and  of  all  ring  systems  these  appear  to  be  the  most  readily 
formed,  the  most  stable,  and  of  the  most  frequent  occurrence  in 
nature.  Without,  therefore,  a  definite  position  and  direction  of  the 

1  It  is  for  this  and  other  reasons  that  some  chemists,  notably  Lessen  (Annalen, 
1880,  204,  295),  Hinrichsen  (Ueber  den  gegenwdrtigen  Stand  der  Valenzlehre\  and 
Werner  (Neuere  Anschauungen  aufdem  Gebiete  der  anorganischen  Chemie),  have  refused 
to  accept  this  method  of  denoting  unsaturation. 


EVIDENCE   OF  STEREOCHEMISTRY  77 

force  of  affinity,  the  theory  of  stereochemistry  in  its  relation  to  stereo- 
isomers  and  ring  formation  would  have  to  be  modified,  if  not  relin- 
quished. 

The  Theory  of  Free  Valencies.  The  theory  of  free  valencies, 
which  was  at  one  time  adopted  by  Fittig  to  explain  the  isomerism  of 
maleic  and  fumaric  acid,  has  been  recently  revived  by  Hinrichsen,1 
who  considers  that  the  nature  of  unsaturation  of  ethylene  compounds 
in  no  way  differs  from  that  of  compounds  containing  bivalent  carbon 
(p.  65).  They  form  additive  compounds  with  the  same  class  of 
reagents  and  under  similar  conditions,  and  therefore,  if  substances 
like  carbon  monoxide,  the  isocyanides,  fulminic  acid,  and  triphenyl- 
methyl  contain  free  valencies,  there  is  no  reason  why  ethylene  should 
be  denied  this  attribute. 

It  is  true  that  the  non-existence  of  isomeric  ethylenes  and  propy- 
lenes  is  not  very  easily  accounted  for, 

CHjj         — C  Ho        CHg 

— CH2  CH3  -CH  CH2      >C 

— CH2          >CH  —  CH2         — CH2        CH. 

Ethylenes.  Propylenes. 

but  the  absence  of  the  radical  CH3  Hinrichsen  regards  as  no  more 
remarkable  than  that  of  PH2  or  NH4.  As  the  electrochemical 
character  of  elements  becomes  more  emphasized  in  their  lower 
valency  combinations  without  having  recourse  to  multiple  linkages 
(e.g.  chlorine  in  HC1  is  more  electronegative  than  in  C102),  so  the 
electronegative  character  of  unsaturated  carbon  is  accentuated  in 
acetylene,  in  which  hydrogen  is  replaceable  by  metals,  and  multiple 
linkage  may  be  equally  dispensed  with. 

Stereoisomerism,  which  might  present  a  difficulty,  is  explained  by 
adopting  Knoevenagel's  view2  of  the  constitution  of  carbon  com- 
pounds in  which  carbon  and  attached  atoms  or  groups  in  saturated 
compounds  occupy  the  faces  of  the  tetrahedron  and  not  the  points, 
whilst  in  ethylene  compounds  the  two  tetrahedra  are  pivoted  on  an 
edge  and  oscillate  backwards  and  forwards,  addition  taking  place  on 
opposite  faces  at  the  extreme  of  an  oscillation  on  one  side  or  the 
other.  In  opposition  to  this  view  it  is  contended  that  if  a  compara- 
tively stable  compound  like  ethylene  possesses  free  valencies,  there  is 
no  reason  why,  for  example,  an  isomeric  propylene  CH2 .  CH2 .  CHa 
should  not  exist. 

Now  although  the  balance  of  evidence  would  appear  to  favour  the 
1  Annalen,  1904,  336,  2:23.  *  Amwkn,  1900,  311,  194. 


78  THE  VALENCY  OF  CARBON 

existence  of  double  bonds  in  unsaturated  compounds,  nevertheless 
certain  recent  observations  have  been  recorded  which  seem  capable 
of  no  other  simple  interpretation  than  the  assumption  of  free 
valencies. 

The  facts  are  briefly  as  follows :  in  1905  Thorpe  and  Rogerson l 
obtained  two  esters  having  entirely  distinct  properties,  to  which  the 
following  formulae  were  assigned  : 

R02C .  C(CN) .  C  =  CH .  C02R    R02C .  CH(CN)  .0=0.  C02R 


OH,       0] 


.  CH3CH3 

The  two  esters  on  hydrolysis  yielded  one  and  the  same  a/3-dimethyl- 
glutaconic  acid,  that  is,  the  two  groupings  are  identical. 
a       0         7  a        /3       7 

—  CH—  C  =  CH—  —  H2C-C  =  C— 

i  1  ii 

Identity  was  also  found  to  exist  in  the  following  pairs  :  a-  and 
y-methylglutaconic  acids  and  the  a-methyl-y-ethyl  and  a-ethyl- 
y-methyl-glutaconic  acids.  In  other  words,  the  a  and  y  positions  are 
identical,  no  doubt  for  the  same  reason  that  determines  the  equality 
.of  the  two  meta  positions  in  the  benzene  ring  and  the  identity  of 
compounds  described  under  virtual  tautomerism  (Part  II,  p.  327). 

Two  explanations  might  be  given  of  the  cause  of  this  identity  in 
the  a  and  y  positions  :  a  dynamical  one,  based  on  the  assumption 
that  the  free  hydrogen  atom  oscillates  between  the  a  and  y  positions 
with  recurrent  change  of  linkage,  or  a  statical  one,  in  which  the 
atomic  arrangement  is  fixed  and  symmetrical,  a  condition  which 
would  involve  the  conception  of  free  valencies  of  the  end  carbon 
atoms  or,  what  amounts  to  the  same  thing,  the  presence  of  two 
tervalent  carbon  atoms. 

The  two  views  may  be  expressed  thus  : 

>C.C.C<  \C-CH—  C< 


In  1909  Feist2  prepared  a  second  and  labile  a-methylglutaconic 
acid  which  at  first  sight  points  to  the  existence  of  cis-  and  trans- 
isomerism  and  was  so  regarded  by  its  discoverer,  and  the  fact 
appeared  to  be  confirmed  by  the  preparation  of  other  a-  and  /?- 
monoalkyl,  a/?-  and  ay-dialkyl-,  and  a/?y-trialkyl-glutaconic  acids  in 
isomeric  forms.3  Were  this  a  case  of  geometrical  isomerism,  it 
would  dispense  at  once  with  both  the  foregoing  explanations. 

1  Trans.  Chem.  Soc.,  1905,  87,  16G9,  1685.  2  Annalen,  1909,  370,  41. 

3  Thorpe  and  Thole,  Trans.  Chem.  Soc.,  1911,  99,  2187. 


THE   THEORY   OF   FREE   VALENCIES  79 

The  inadequacy  of  the  stereoisomeric  explanation  has  been  placed 
in  a  very  clear  light  by  Thorpe  and  his  collaborators.  a-Alkylgluta- 
conic  acid  may  be  taken  as  a  typical  case.  It  is  converted  on  treatment 
with  acetyl  chloride  into  an  anhydride,  which  acts  as  a  monobasic 
acid.  It  forms  well-crystallised  alkali  salts  from  which  acids  liberate 
the  original  anhydride  ;  it  yields  an  acetyl  derivative,  and  with 
phosphorus  chloride,  hydroxyl  is  replaced  by  chlorine. 

When  hydrolysed  with  strong  potassium  hydroxide  solution  or  by 
dilute  alkali  carbonate  in  presence  of  casein  l  the  anhydride  passes 
into  the  salt  of  the  labile  acid,  which  is  rapidly  converted  by  boiling 
with  hydrochloric  acid  into  the  stable  acid. 

The  process  of  formation  and  acid  properties  of  the  anhydride 
point  unmistakably  to  one  of  the  following  formulae  : 

—  CO  /CR:C(OH) 

HC<  >0 


DH:C(OH)  ^CH.CO 

i.  ii. 

that  is,  the  free  hydrogen  atom  of  the  three-carbon  system  passes  to 
the  oxygen,  forming  a  hydroxyl  group.  Of  the  two,  the  first  formula 
is  preferred  owing  to  the  absence  of  pyruvic  acid  among  the  products 
of  oxidation,  which  the  second  might  be  expected  to  yield.  Now  in 
the  conversion  of  the  alkali  salt  of  the  hydroxy-anhydride  into  the 
salt  of  the  labile  acid  and  the  latter  into  the  stable  acid,  the  follow- 
ing changes  will,  according  to  Thorpe,  occur  : 

^CR—  CO  ,CR  .  COOH  -,CR  .  COOH 

HOC  >°       ->     HCC  ->     HaC< 

\CH  :  C(OH)  \CH2  .  COOH  -^CH  .  COOH 

Hydroxy-anhydride.  Labile  acid.  Stable  acid. 

The  different  alkylglutaconic  acids  examined  appear  to  behave 
much  in  the  same  way,  and  differ  mainly  in  the  stability  of  the 
hydroxy-anhydride  and  the  labile  forms  of  the  acids  which  are 
greatly  influenced  by  the  position  of  the  alkyl  group.  Glutaconic 
acid  itself,  though  it  gives  a  hydroxy-anhydride,  forms  no  labile 
isomer.  But  what  evidence  is  there  for  the  existence  of  two 
structural  rather  than  of  two  geometrical  isomers  ? 

The  evidence  is  briefly  as  follows  :  2  glutaconic  ester  and  its  alkyl 
derivatives  containing  a  mobile  hydrogen  atom,  when  treated  with 
sodium  ethoxide,  give  yellow  sodium  ethoxide  compounds.  When 

1  Casein  in  small  quantity  acts  as  an  '  anticatalyst  '.     After  treatment  with 
dilute  alkali  the  acid  is  converted  into  the  silver  salt  from  which  H2S  liberates 
the  labile  acid.     With  strong  potash  the  dipotassium  salt  of  the  labile  acid  is 
formed. 

2  Thorpe  and  Bland,  Trans.  Chem.  Soc.,  1912,  101.  871. 


80  THE  VALENCY  OF  CARBON 

the  sodium  compound  is  decomposed  by  water  the  first  product 
according  to  Thorpe  must  be  the  ester  of  the  labile  acid,  a  portion  of 
which,  according  to  the  varying  stability  of  the  acid,  would  pass  into 
the  stable  ester. 


— RC .  CO.C2H5  RC .  C02C2H5 

CB2  «-  CH 

— CH  .  C02C2H5  CH2 .  C02C2H5 

Stable  ester.          \  f       Labile  ester. 

RC .  C02C2H5 

CH 

|  /ONa 

CH: 


Sodium  ethoxide  compound. 

The  two  esters  cannot  however  be  distinguished,  since  they  are 
both  insoluble  in  alkaline  solution.  But  by  introducing  two  negative 
groups  into  the  group  carrying  the  acid  hydrogen,  the  sodium 
compound  is  thereby  rendered  more  stable  in  aqueous  solution  and 
can  be  separated  from  the  normal  ester  produced  at  the  same  time  by 
extracting  the  latter  with  ether. 

R.C.C02C2H5  R.C.C02C2H5 

CH2  «-  CH 

I  I 

C2H502C  .  C  .  C02C2H5  C2H5OCO  .  C  :  C/ 

Stable  ester.  Sodium  ethoxide  compound. 

R  .  C  .  C02C2H5  R  .  C  .  C02C2H5 

->  CH  -»  CH 


,ONa 


OC2H5 


C2H502C  .  C  :  C<  C2H502C  .  CH  .  C02C2H5 

\OC2H5 

Labile  enol  ester.  Labile  keto  ester. 

From  the  sodium  compound  which  is  present  in  the  enolic  form 
carbon  dioxide  liberates  the  labile  ketonic  compounds.  The  above 
process  has  been  carried  out  in  the  manner  described  with  the 


THE  THEORY  OF  FREE  VALENCIES  81 

carbethoxy-derivatives  of  a-methyl,  ethyl,  and  benzyl-glutaconic 
esters  and  in  each  case  a  labile  ester  was  isolated  in  enol  and  keto 
forms  which  underwent  conversion  into  the  stable  ester. 

The  discovery  of  a  third  isomer  of  /?-phenyl-a-methylglutaconic  acid 
has  afforded  the  final  proof  of  Thorpe's  view.1 

In  the  process  of  synthesizing  the  ester,  two  forms  were  obtained, 
a  liquid  and  a  solid,  corresponding  probably  to  the  cis  and  trans 
isomer  (see  Part  II,  p.  243).  When  the  liquid  ester  is  hydrolysed 
it  yields  two  acids  which,  according  to  Thorpe,  represent  the 
normal  and  cis  acids,  whilst  the  solid  ester  only  gives  one 
product. 

If  the  hydroxy-anhydride,  obtained  as  previously  described,  is  boiled 
with  water,  it  is  converted  into  the  normal  acid  :  if  treated  with  con- 
centrated alkali,  it  forms  a  mixture  of  the  normal  and  cis  acids; 
finally,  if  acted  on  with  dilute  alkali  in  presence  of  casein,  only  the 
cis  acid  is  obtained.  Again,  the  trans  acid  may  be  converted  into 
the  cis  acid  by  the  action  of  alkali,  whilst  the  latter  passes  into  the 
hydroxy-anhydride  with  acetyl  chloride.  So  far  no  method  has  been 
devised  for  converting  the  cis  and  normal  acid  into  the  trans  modifica- 
tion. This  close  connexion  between  the  three  compounds  is  further 
illustrated  by  the  fact  that  all  three,  when  boiled  with  mineral  acids, 
give  the  same  isobutenylbenzene,  CH3 .  CH  :  C(C6H5)CH3. 


CH3.C.C02H 

C6H5.CH 

+\P 
CH3.C — CO          vX         HC.C02H  \'       CH3.C.C02H 

C6H5.C  \0  Normal^.  C6H5 .  C 

CH:C(OH)    ^         CH3.C.C02H      ^    C02H.CH2 

Hydroxy-anhydride.  \5^v  -Ay  /  Trans  acid. 

C6H5.C 


CII2. 


C02H 


Cis  acid. 


A  very  similar  series  of  experiments  conducted  by  Thorpe  and 

1  Thorpe  and  Wood,  Trans.  Chem.  Soc.,  1913.  103,  1569. 
FT.  J  O 


82  THE  VALENCY  OF  CARBON 

Bland1  on  aconitic  acid  has  revealed  the  existence  of  stable  and  labile 
forms  of  this  acid,  which  the  authors  represent  by  the  following 
formulae : 

— CH .  C02H  CH .  C02H 


CH.COoH  C. 


C02H 


I  I 

— CH.C02H  CH2.C02H 

Stable.  Labile. 

Aconitic  acid. 

In  this  case  the  labile  acid  is  a  comparatively  stable  substance, 
which  differs  from  the  normal  acid  in  its  melting-point  and  in  its 
behaviour  with  acetyl  chloride.  Whereas  pure  acetyl  chloride  free 
from  phosphorus  chloride  gives  no  anhydride  with  the  ordinary  acid, 
the  labile  modification  is  converted  by  both  the  pure  and  impure 
reagent.  No  attempt,  it  seems,  has  .been  made  to  determine  the 
nature  of  the  bromine  addition  products. 

Werner's  Theory  of  Uusaturatiou.  This  theory,  which  is  dis- 
cussed on  p.  90  in  connection  with  Werner's  theory  of  valency,  repre- 
sents the  force  of  affinity  as  emanating  from  the  centre  of  a  spherical 
atom  and  distributing  itself  evenly  over  the  surface.  The  distribu- 
tion may,  however,  change  according  to  the  nature  of  the  attached 
atoms.  In  methane,  where  the  atoms  linked  to  the  central  carbon 
atom  are  the  same,  the  amount  of  valency  is  evenly  distributed 
among  the  four  hydrogen  atoms.  In  the  case  of  a  substance  such  as 
ethylene,  the  attached  carbon  atoms  command  a  certain  larger  share 
of  affinity.  This  larger  share  of  affinity  would  appear  at  first 
sight  to  have  the  effect  of  binding  the  unsaturated  carbon  atoms 
more  firmly  than  the  smaller  amount  demanded  by  the  saturated 
atoms.  The  explanation  of  this  apparent  paradox  is  given  on 
p.  86.  The  phenomenon  of  geometrical  isomerism  as  explained  by 
Werner's  theory  has  been  discussed  at  length  in  Part  II,  p.  258. 
There  only  remains  the  application  of  the  theory  to  ring  structures, 
and  it  must  be  confessed  that  this  is  its  weakest  point.  Werner's 
theory  affords  no  satisfactory  explanation  of  the  peculiar  stability  of 
five-  and  six-atom  rings;  on  the  contrary,  the  very  reverse  effect 
would  be  anticipated,  that  is  to  say,  the  carbon  atoms  when  most 
closely  in  contact,  and  whose  affinities  would  therefore  be  most 
completely  neutralised,  should  offer  the  greatest  stability,  and  this 
would  necessarily  exist  in  the  smaller  and  not  the  larger  ring 
formations. 

1  Trans.  Chem.  Soc.,  1912,  101,  1490. 


EQUIVALENCE  OF  THE  CARBON  BONDS  83 

Equivalence  of  the  Carbon  Bonds.  An  attempt  has  been  made 
to  establish  the  equal  value  of  the  four  carbon  valencies  by  a  method 
which  consists  in  replacing  successively  the  different  hydrogen  atoms 
of  marsh  gas  by  the  same  element  or  group  and  comparing  the 
products  in  each  case  on  the  assumption  that  during  interchange  of 
constituents  no  migration  occurs.  Henry l  succeeded  in  converting 
methyl  iodide  into  methyl  cyanide  by  four  different  methods,  and  in 
such  a  manner  that  a  different  atom  of  hydrogen  in  the  original 
compound  was  replaced. 

The  following  scheme,  which  need  not  be  described  in  detail,  will 
indicate  the  nature  of  the  process : 
CH3I-»CH3CN 


CH3 .  COOH  -*  CH2C1 .  COOH  -> 
CH2CN .  COOH  -*  CH3CN 

CH2(COOH)2  -»  CHC1(COOH)2  ->  CH2C1 .  COOH  -»  CH3CN 

CClNa(COOH)2  -»  CC1(COOH)3  -» 

CH2C1COOH  ->  CH,CN 

Equivalence  determined  in  this  way  does  not  necessarily  imply 
that  each  of  the  residual  hydrogen  atoms  retains  its  original  value 
after  substitution  has  taken  place,  that  is,  keeps  its  original  properties. 
In  all  probability  quite  the  contrary  is  the  case  and,  according 
to  the  nature  of  the  substituent,  the  remaining  hydrogen  atom  or 
atoms  become  more  or  less  mobile,  or,  to  put  it  broadly,  every  new 
substituent  changes  the  character  of  the  molecule. 

Theories  of  Valency.  We  will  conclude  this  account  of  the 
valency  of  carbon  by  a  brief  summary  of  the  more  common  theories 
of  valency. 

The  recognition  of  different  degrees  of  affinity  in  the  formation  of 
compounds  of  definite  composition  runs  through  the  whole  history 
of  modern  chemistry.  It  appears  in  Berzelius'  electrochemical  theory 
applied  to  compounds  of  the  first,  second,  and  third  order,  when,  for 
example,  a  metal  combines  with  an  oxide,  a  basic  with  an  acid 
oxide,  and,  finally,  when  two  metallic  salts  unite  to  form  alums  and 
other  double  salts  (see  p.  6),  and  it  is  clearly  brought  out  in 
the  principal  and  auxiliary  valencies  of  Werner  (p.  90),  in  the 
normal  and  contra- valencies  of  Abegg  and  Bodlander  (p.  58),  and  in 

1  Compt.  rend.,  1887,  104,  1106  ;  Zeit.  physik.  Chem.,  1888,  2,  553  ;  Bull.  Acad.  roy. 
Belg.,  1906  (3),  12,  644;  15,333;  see  also  E.  Fischer  and  Brieger,  Ber.,  1915,48,  1517. 

a  2 


84  THE  VALENCY  OF  CARBON 

the  partial  and  residual  valencies  of  other  writers.  The  designation 
of  unit  of  valency  by  a  bond  has,  moreover,  proved  so  serviceable  in 
organic  chemistry  as  to  become  an  almost  indispensable  system 
in  expressing  the  structure  of  compounds.  If  it  is  once  admitted 
that  valency  may  vary  in  strength  as  well  as  in  number,  the  way  is 
open  for  the  creation  of  a  variety  of  kinds  of  linkage.  Recent  years 
have  witnessed  the  introduction  of  centric  and  zigzag  bonds  and 
dotted  or  partial  valencies  to  denote  affinities  of  a  special  kind.  These 
symbols,  it  is  true,  are  only  used  to  interpret  certain  phenomena ; 
but  they  tacitly  imply  a  difference  in  the  nature  of  the  force  of 
affinity  for  which  there  appears  to  be  no  sufficient  justification. 

The  theories  of  valency  may  for  convenience  be  divided  into  those 
which  are  associated  with  certain  physical  properties,  those  which 
serve  to  explain  the  character  of  the  phenomenon,  and  those,  mainly 
electrochemical,  which  attempt  to  define  the  cause. 

Valency  and  Physical  Properties.  Mendeleeff  and  Lothar  Meyer 
showed  that  valency  and  physical  as  well  as  chemical  properties 
were  periodic  functions  of  the  atomic  weight  of  the  elements.  The 
relation  of  valency  to  atomic  volume  in  compounds  has  been  further 
developed  by  Barlow  and  Pope,  Le  Bas  and  Richards,  whilst  Traube 
has  attempted  to  establish  its  connection  with  refractivity.  Barlow 
and  Pope l  suppose  that  each  atom  occupies  a  certain  space  or  'sphere 
of  influence '.  These  units  form  aggregates  which  constitute  the 
chemical  molecule,  and  in  a  solid  the  crystal  form  is  determined  by 
the  closest  possible  packing  of  the  aggregate  spheres.  The  under- 
lying principle  of  the  theory  is  that  the  volumes  of  these  spheres  are 
determined  by  and  proportional  to  the  fundamental  valencies  of  the 
atoms,  and  may  be  called  the  valency  volumes.  Thus,  atoms  of  equal 
valency  volume  may  replace  one  another  without  changing  the 
predominant  character  of  the  crystal  form,  although  variations  in 
the  ratio  of  the  axes  may  occur. 

A  similar  theory  has  been  propounded  by  Le  Bas,2  who  has  shown 
that  the  molecular  volume  at  the  melting-point  of  a  series  of  paraffins 
divided  by  the  total  valency  of  the  atoms  gives  a  mean  value  of  2-97. 
This  represents  the  unit  valency  volume.  Now  the  difference  in 
valency  value  between  each  member  of  the  series  is  6,  that  is,  the 
valency  value  of  CH2,  and  consequently  the  valency  volume  is 
6  x  2-97  =  17-82,  whereas  the  mean  difference  in  molecular  volume 
actually  observed  is  17-83  and  is,  therefore,  in  complete  accord  with 
the  theoretical  value.  The  fundamental  idea  is  not  new.  Similar 

1  Trans.  Chem.  Soc.,  1906,  89,  1675. 

2  Trans.  Chem.  Soc..  1907.  91«  112  ;  see  also  Part  II,  p.  6. 


VALENCY  AND  PHYSICAL  PROPERTIES  85 

views  were  advanced  by  Kopp  from  observations  on  the  atomic  and 
molecular  volumes,  and  also  by  Schroeder,  who  introduced  the  idea 
of  unit  atomic  volume  or  stere.  Traube1  has  also  pointed  out 
that  the  atomic  refractivities  for  the  Ha  line  for  C,  N,  0,  and  H  is  in 
the  ratio  of  4 : 3  : 2  : 1.  If  the  unit  valency  value  is  0-787,  then  the 
molecular  refractivity  should  be  this  number  multiplied  by  the 
number  of  valencies.  Normal  pentane  with  32  valency  units  has  a 
Ma  =  25  32,  equal  to  that  of  valeric  aldehyde  Ma  =  25-31  with  the 
same  number  of  valency  units. 

Richards  2  regards  the  atoms  as  mutually  compressing  one  another 
either  by  force  of  attraction  or  by  cohesion,  and  has  determined  the 
diminution  of  volume  which  liquids  and  solids  undergo  by  com- 
pression. On  the  assumption  that  in  both  physical  states  the  atoms 
are  closely  packed,  he  attributes  the  amount  of  the  compression  to 
the  diminution  of  space  occupied  by  the  atoms  themselves,  and  not 
to  that  of  the  intervening  spaces.  There  are,  consequently,  two 
forces  which  determine  this  compression,  namely,  cohesion  and 
attraction,  and  he  explains  in  this  way  the  tetrahedral  form  of  the 
asymmetric  carbon  atom  by  the  unequal  compression  produced  by 
the  four  different  groups  on  the  surface  of  the  atom. 

Theories  of  Valency  (Werner's  Theory 3).  Werner's  theory  of 
valency  possesses  the  attribute  of  simplicity.  According  to  this 
view,  which  is  based  upon  that  of  Glaus,4  valency  is  a  property 
of  attraction  which  emanates  from  the  centre  of  an  atom  and  is 
evenly  distributed  over  the  surface.  The  shape  of  the  atom  is  of  no 
moment  as  it  is  in  constant  motion,  but  it  may  be  regarded  as 
spherical.  In  the  union  of  an  atom  with  the  maximum  number  of 
other  atoms,  the  latter  will  distribute  themselves  so  as  to  produce 
the  greatest  neutralisation  of  their  reciprocal  affinities  and  the 
surface  attraction  will  divide  itself  among  the  atoms  according  to 
their  nature.  The  most  stable  arrangement  will  be  that  in  which 
the  largest  surface  of  the  central  sphere  is  covered  without  over- 
lapping. This  is  taken  to  explain  the  difference  in  maximum  valency 
manifested  by  sulphur  and  phosphorus  in  their  union  with  the 
halogens,  the  lighter  halogen  atoms  being  present  in  largest  number. 
SFC  SC14  SBr2 

PC15    PI3 
It  accounts  also  for  the  existence  of  triphenylm  ethyl,  but  not  of 

1  Ber.,  1907,  30,  723.  2  Trans.  Ohem.  Soc.,  1911,  99,  1201. 

*  Neuere  Anschauungen  avf  dem  Gebiete  der  anorganischen  Chemie,  by  A.  Werner. 
Vieweg,  Brunswick,  1909. 
4  Ber.,  1881,  14,  432. 


86  THE  VALENCY  OF  CARBON 

CH3,  for  in  the  former  the  heavier  group,  like  the  heavier  halogen, 
appropriates  more  valency.  If  all  the  four  atoms  attached  to  carbon 
are  similar,  as  in  methane,  they  will  monopolize  an  equal  amount  of 
surface-attraction  and  arrange  themselves  in  the  form  of  a  regular 
tetrahedron.  If  some  of  the  atoms  are  different  the  distribution  of 
affinity  will  be  irregular,  and  if  all  four  are  different  an  asymmetrical 
tetrahedral  grouping  will  result. 

Werner  applies  his  theory  to  the  union  of  two  carbon  atoms  in 
the  following  manner.  The  full  force  of  affinity  will  only  be  exerted 
at  the  points  of  contact  of  the  two  carbon  atoms,  and  at  every  other 
point  on  the  hemispheres  the  strength  of  affinity  will  be  the  resultant 
of  the  force  emanating  from  the  centre  and  parallel  to  the  line 
joining  the  centres  of  the  two  spheres.  In  Fig.  2  the  force  of  affinity 
at  the  point  where  the  dotted  line  meets  the  circumference  of  the 


FIG.  2. 

sphere  may  be  resolved  into  the  two  forces  a  and  1),  of  which  only  a 
will  be  active  in  binding  the  two  carbon  atoms. 

The  force  gradually  falls  away  as  the  distance  between  the  surfaces 
increases,  thus  leaving  an  amount  of  free  affinity  which  has  been 
estimated  at  less  than  one-half  and  more  than  one-third  of  the  total 
affinity  required  for  binding  the  other  atoms. 

The  case  of  unsaturated  carbon  has  already  been  dealt  with  (pp.  59, 
65),  and  in  this  case  the  amount  of  free  affinity  is  calculated  as  nearly 
equivalent  to  that  which  is  bound.  By  a  similar  disposition  of  two 
spheres  Werner  represents  trebly-linked  carbon  in  the  acetylene 
series;  but  as  only  one  other  atom  is  attached  to  each  sphere  the 
amount  of  affinity  left  for  binding  the  two  carbon  atoms  is  greater 
than  that  used  for  either  a  singly-  or  doubly-linked  system.  It  thus 
appears  as  if  more  affinity  were  employed  in  joining  unsaturated 
carbon  atoms  than  those  in  which  there  is  a  single  linkage.  To 
explain  this  apparent  paradox  Werner  draws  a  distinction  between 
stability  and  reactivity.  This  reactivity  is  determined  by  the  amount 


THEORIES  OF  VALENCY  87 

of  the  component  6,  Fig.  2,  which  Is  larger  in  ethylene  and  acety- 
lene than  in  ethane  derivatives,1  and  serves  to  attach  other  atoms, 
thus  rendering  the  unsaturated  compound  more  sensitive  to  chemical 
action.  On  the  basis  of  this  general  conception  Werner  has  elaborated 
a  theory  which  explains  among  other  things  those  complex  struc- 
tures commonly  known  as  molecular  compounds.  As  the  application 
of  these  principles  is  mainly  concerned  with  inorganic  compounds 
we  have  given  a  brief  summary  of  the  latter  on  p.  90. 

The  idea  of  a  maximum  of  disposable  affinity  which  may  be 
differently  distributed  according  to  the  nature  of  the  union  has 
been  utilized  by  Flurscheim  2  to  explain  certain  apparent  anomalous 
affinity  constants  among  the  organic  acids  and  bases.  The  theory 
has  been  embodied  in  the  following  proposition  :  '  The  strength  of 
a  chemical  bond  is  a  function  of  the  disposable  amount  of  chemical 
force  in  atoms  and  also  of  the  polar  nature  of  that  force.'  It  is 
found,  for  example,  that  the  unsaturated  aliphatic  acids  have  the 
following  values  for  K : 


Valeric  acid 
a)3  Pentoic   ,, 

Py      »       » 

75         »         »> 

K 

0-00165 
0-00148 
0-00335 
0-00209 

n.  Hexoic  acid 
a/3  Hexenic   „ 
07          „         ,t 
75           u         » 
8«           t.         it 

K 

0-00146 
0.00189 
0-00264 
0-00174 
0-00191 

It  is  not  obvious  why  the  /?y  acid  in  the  above  series  should  have 
the  highest  value  or  why  the  second  and  fourth  member  in  the 
second  series  should  be  higher  than  the  first  and  third;  but  if  the 
distribution  of  affinity,  as  determined  by  electrochemical  relations, 
is  taken  into  account,  the  reason  is  plain.  For  according  to 
Flurscheim  the  strength  of  the  acid  is  determined  by  its  affinity 
constant  or  the  mobility  of  the  hydrogen  atom  or,  in  other  words, 
by  the  weakness  of  its  attachment  or  that  of  the  electron  (see  p.  96) 
to  the  oxygen  of  the  carboxyl  group.  The  double  bond  does  not 
utilize  the  full  measure  of  two  whole  valencies  of  the  atoms  involved, 
which  are  consequently  able  to  part  with  an  extra  share  to  the 
adjoining  atoms.  If  the  distribution  is  represented  by  thin  and 
thick  lines  the  formulae  will  take  the  following  form : 

jO 

a/3    K.CHiCH— C<  weaker  acid 

\0-H 


C, 


R .  CH  :  CH—  CH2— C<  stronger  acid 

-H 

1  Ber.,  1906,  30,  1278.        »  Trans.  Chem.  Soc.,  1909,  95,  718. 


88  THE  VALENCY  OF  CARBON 

/O 

yS    R.CH:CH—  CH2-CH2—  C<  weaker  acid 

X)—  H 

Se      R  .  CH  :  CH—  CH2-CH2-CH2-C^  stronger  acid 

X>-H 

The  same  idea  may  serve  to  explain  why  the  meta-,  chloro-,  and 
bromo-benzoic  acids  have  a  higher  affinity  constant  than  the  para 
compounds. 


-H 

Cl 

K  =  0-0155  K  =  0-0093 

Similarly  tetraethylammonium  hydroxide  is  a  stronger  base  than 
triethylstannic  hydroxide,  for  the  affinity  between  the  electronegative 
nitrogen  and  the  electropositive  alkyl  groups  is  stronger  than  that  of 
tin.  Hence  ionisation  takes  place  more  readily  in  the  former  case. 

*H5  /c*H--> 

£5  HO—  Sn^-C2H3 

A  \0  H 

2H5  b2t±5 

Tschitschibabin  x  shares  the  general  ideas  of  Werner  and  Fliir- 
scheim,  and  like  them  discards  the  theory  of  multiple  bonds.  He 
distinguishes  between  valency  or  maximum  combining  capacity  and 
atomicity  or  actual  binding  capacity  (Bindefiihigkeit),  which  may  be 
anything  less  than  the  maximum,  and  being  graduated  cannot  have 
a  definite  value  nor  be  indicated  by  bonds.  In  unsaturated  com- 
pounds, such  as  ethylene,  carbon  is  triatomic,  in  acetylene  and 
carbon  monoxide  it  is  monatomic.  The  more  atoms  the  original 
atom  can  attach,  the  more  saturated  it  is,  the  various  degrees  of 
unsaturation  depending  partly  upon  the  degree  of  unsaturation 
of  the  attached  atoms,  partly  on  the  mass  of  the  attached  radicals, 
and  partly  on  the  opposite  electrochemical  character  of  the  two. 

That  the  degree  of  unsaturation  varies  is  shown  by  the  varying 
value  of  the  heat  of  combustion  of  the  unsaturated  carbon  in  ethylene 
compounds2  and  their  very  different  affinity  for  bromine,  &c.,  as 
shown  by  Bauer  (see  p.  116).3  Triatomic  carbon  in  ethylene  by 
being  joined  to  triatomic  carbon  would  be  more  saturated  than 
methyl  ;  in  the  same  way  triatomic  carbon  is  more  saturated  by  being 

1  J.  prakt.  Chem.,  1912,  86,  381. 

2  Swientoslawsky,  Zeit.  physik.  Chem.,  1909,  65,  513. 
8  Bauer,  J.  prakt.  Chem.,  1905,  72,  206. 


THEORIES  OF  VALENCY  89 

joined  to  two  triatomic  groups  than  to  one.    In  butadiene  the  carbon 
atoms  2  and  3  are  more  saturated  than  1  and  4. 

1234 
CH2— CH-CH— CH2 

In  diphenylbutadiene  the  atoms  1,  4  being  attached  to  heavier 
radicals  are  more  saturated  than  1  and  4  in  butadiene,  and  so  forth. 
On  this  principle  a  number  of  interesting  facts  are  explained,  such  as 
Thiele's  rule  (see  p.  133)  and  the  existence  of  triphenylmethyl,  the 
stability  of  which  is  ascribed  to  saturation  produced  by  the  attach- 
ment of  the  central  carbon  to  three  heavy  radicals  by  the  three 
triatomic  carbon  atoms  of  the  benzene  nuclei. 

The  theory  also  accounts  for  the  saturated  character  of  benzene, 
since  the  system  consists  of  triatomic  carbon  atoms  which  produce 
a  high  degree  of  mutual  saturation.  It  explains  also  the  unsaturated 
nature  of  tetrahydrobenzene  and  also  the  greater  unsaturation  of  the 
a  as  compared  with  the  /?  and  central  carbon  atoms  in  naphthalene, 
and  consequent  greater  reactivity  of  the  former,  for  the  two  central 
carbon  atoms  are  each  joined  to  three  triatomic  carbon  atoms,  whilst 
the  ft  carbon  atoms  are  joined  to  two.  The  a  carbon  atoms,  on  the 
other  hand,  are  linked  to  one  ordinary  triatomic  carbon  and  to  one 
central  carbon  atom,  which,  being  highly  saturated,  cannot  greatly 
increase  the  saturation  of  the  a  carbon,  which  is  the  least  saturated 
of  the  three.  The  theory  also  serves  to  explain  the  rules  of  substitu- 
tion in  aromatic  compounds,  and  is  referred  to  on  p.  149. 

But  it  takes  little  account  of  stereoisomerism,  the  essence  of  which 
lies  in  the  definite  geometrical  relations  of  the  attached  atoms  or 
groups  round  the  central  carbon  atom,  or  atoms,  for  which,  if  for  no 
other  purpose,  the  mechanical  device  of  bonds  has  proved  so  fertile, 
nor  of  the  nature  of  ring  structure,  which,  as  already  stated,  requires 
a  definite  disposition  of  the  carbon  valencies. 

Wunderlich,1  whose  views  bear  an  outward  resemblance  to  those  of 
van 't  Hoff,  represents  the  carbon  atom  as  a  tetrahedron  circumscribed 
round  a  sphere  ;  but  the  points  of  attraction  are  conceived  as  con- 
centrated at  the  centres  of  the  four  faces,  so  that  a  singly  linked  atom 
will  be  attached  to  the  face  and  not  to  the  corner  of  a  tetrahedron. 
In  this  way  the  stability  of  the  single  bond  will  correspond  to  its 
geometrical  form. 

In  unsaturated  compounds  the  carbons  are  represented,  as  in  van  't 
Hoff  s  arrangement,  by  the  edges  of  two  tetrahedra,  but  in  conse- 
quence of  the  points  of  attraction  being  situated  at  the  centre  of  the 
tetrahedral  faces,  the  forces  joining  the  two  carbon  atoms  aai  (Fig.  3) 
1  Konfiguration  organischer  Molekiile,  Wiirzburg,  1886. 


90  THE  VALENCY  OF  CAKBON 

will  be  the  resultant  of  the  two  pairs  of  forces  Ic  and  fc^,  leaving 
a  residue  of  affinity  de  and  dfa,  which  may  correspond  to  Thiele's 
partial  valencies  (see  p.  133). 

A  similar  view  has  been  adopted  by  Knoevenagel,  and  has  already 
been  referred  to  (p.  77). 

Werner's  Theory  of  Valency l  (Molecular  compounds).  As  we 
have  seen  in  a  previous  section  (p.  82),  Werner  regards  the  valency 
of  each  atom  as  distributing  itself  according  to  its  spatial  arrange- 
ments and  its  degree  of  affinity  towards  contiguous  atoms.  Compounds 
are  thus  formed  of  tJie  first  order,  which  do  not  necessarily  exhaust 
the  amount  of  affinity  at  the  disposal  of  the 
atoms  in  question.  This  residual  valency  can 
attach  other  atoms,  and  so  form  compounds  of 
the  second  order.  In  developing  this  conception 
Werner  has  introduced  the  terms  principal  and 
auxiliary  valencies  to  denote  the  above  two 
kinds  of  attachment.  The  principal  valencies 
correspond  to  our  ordinary  valencies  and  bind 
together  atoms  or  groups  whose  saturation 
capacity  may  be  measured  in  terms  of  hydrogen 
atoms.  Such  principal  valencies  are  present  in  FIG  g 

-Cl,     —  Na,     — N02,     — CH3,  &c. 

The  auxiliary  valencies,  which  are  expressed  by  dotted  in  place  of 
straight  lines,  represent  residual  affinities  and  link  together  radicals 
which  can  function  as  separate  molecules.  Such,  for  example,  are  : 

OH,,  NH3,         -C1K,          -CrCl3,  &c. 

The  two  kinds  of  valencies  are  differentiated  by  their  energy  content, 
the  principal  valencies  having  a  greater  affinity  than  the  auxiliary. 
The  difference  is,  however,  one  of  degree  and  determined  by  the 
degree  of  saturation  of  the  other  valencies.  There  is,  in  short,  no 
definite  line  of  demarcation  between  the  two,  but  they  merge  and, 
under  certain  conditions,  pass  into  one  another,  the  auxiliary  becoming 
principal  and  the  principal  auxiliary  valencies. 

For  example,  the  metal  and  oxygen  in  the  oxides  of  the  alkalis 
and  alkaline  earths  are  united  by  principal  valencies  and  form  stable 
oxides,  but  nevertheless  combine  by  their  auxiliary  valencies  with 
water  or  alcohol,  forming  well-defined  and  stable  hydrates  and 
alcoholates,  in  which  the  OH  and  OK  groups  are  linked  by  principal 
valencies. 

1  Neuere  Anschaw.mgen  auj  dem  Geliete  der  anorganischcn  Cliemie,  by  A.  Werner. 
Vieweg,  Brunswick,  1909. 


WERNER'S  THEORY  OF  VALENCY  91 

OH 


BaO     +  -  H90    -»    BaO-HO    ->    Ba 


/ 


In  the  same  way  ammonium  chloride  is  formed  by  union  of  tho 
auxiliary  valencies  of  ammonia  and  hydrogen  chloride. 


C1H—  +  —NH,    -*     C1H    NH,    ->     |         N/      Id 


H\  /n\ 


The  formation  of  methylammonium  iodide  is  produced  in  a  similar 
fashion. 


CH3I     +     NH3    -»    CH3I    NH3    ->    (NH,CH3)I 

The  position  of  the  halogen  outside  the  bracket  is  intended  to 
indicate  a  difference  in  its  attachment  and  to  show  that  it  is  ionised 
in  solution,  as  explained  below. 

The  sulphides  of  arsenic,  antimony,  &c.,  combine  by  their  auxiliary 
valencies  with  alkaline  sulphides,  forming  sulpho-salts  of  considerable 
stability  ;  and  platinum,  palladium,  and  gold  chloride  form  well- 
characterized  salts  with  alkaline  chlorides.  Some  compounds,  indeed, 
increase  in  stability  by  saturation  of  their  auxiliary  valencies. 
Feme  anhydride  is  stable  in  the  ferrates  ;  certain  persalts  are  stable, 
containing  oxides  which  cannot  be  isolated  ;  manganese  tri-  and 
tetra-chloride  are  not  obtainable  in  the  free  state,  but  readily  form 
double  chlorides  and  so  forth. 

From  some  of  the  above  examples  it  will  be  seen  that  the  number 
of  principal  valencies  is  not  a  fixed  quantity,  but  depends  on  the 
nature  of  the  attached  atoms.  With  the  change  in  number  there  is 
a  change  in  strength,  and  a  consequent  variation  in  the  strength  of 
the  valency.  There  is,  however,  a  maximum  number  of  principal  as 
well  as  of  auxiliary  valencies.  Werner  admits  that  the  distinction 
between  the  two  kinds  is  of  a  somewhat  vague  and  indeterminate 
character,  and  is  maintained  *  because  it  seems  necessary  in  the 
present  transitional  state  of  our  views  on  valency  to  mark  out  well- 
defined  areas  on  which  a  more  comprehensive  theory  may  afterwards 
be  erected  '. 

Before,  however,  concluding  this  account  of  the  nature  of  principal 
and  auxiliary  valencies  it  should  be  pointed  out  that  among  the 
characteristics  of  radicals  united  by  principal  valencies  is  their  power 
of  functioning  as  independent  ions,  whereas  those  combined  by 
auxiliary  valencies  lack  this  property.  The  difference  may  be  illus- 
trated in  the  case  of  copper  glycocoll, 


92  THE  VALENCY  OF  CARBON 

CH2.NH2 

COO.  Cu 

in  which  the  copper  forms  an  inner  complex  salt  by  means  of  its 
auxiliary  valency  so  that  in  solution  it  does  not  undergo  ionisation, 
whereas  the  same  metal  attached  by  a  principal  valency  (as  in  copper 
acetate)  is  electrolytically  dissociated.  According  to  the  electronic 
theory  the  atoms  bound  by  principal  valencies  are  characterized 
by  the  mobility  of  their  electrons,  a  feature  which  is  absent  in  those 
radicals  which  are  attached  by  auxiliary  valencies.  Werner  does  not, 
however,  regard  the  two  characteristics  of  principal  valency  attach- 
ment and  electrochemical  behaviour  as  necessarily  interwoven,  but 
only  in  so  far  correlated  that  the  saturation  of  the  affinity  simul- 
taneously loosens  the  electron  from  the  positive  atom  and  so  allows 
it  to  transfer  itself  to  the  negative  component  of  the  salt.  But  the 
saturation  of  a  principal  valency  is  not  always  sufficient  to  produce 
this  effect,  and  in  many  cases  the  saturation  of  auxiliary  valencies  is 
required. 

The  element  of  a  group  which  is  separated  by  ionisation  from  the 
rest  of  the  molecule  is  usually  denoted  by  placing  it  outside  a  bracket. 

Valency  Isomerism.  The  distinction  between  principal  and 
auxiliary  valencies  has  been  made  the  basis  of  a  theory  of  valency 
isomerism1  of  which  the  following  may  serve  as  an  illustration.  Two 
isomeric  methyl  sulphites  have  long  been  known,  both  of  which  are 
principal  valency  compounds : 


/v/v/Aj-2  /V^-LA3 

— x  02S< 

\OCH3  \OCH3 

Recently  E.  Briner  has  obtained  an  isomeric  compound  in  which  the 
two  parts  of  the  compound  are  represented  as  linked  by  auxiliary 
valencies. 


0,8    0 

CH, 

Without  discussing  at  greater  length  Werner's  views,  which  are 
mainly  concerned  with  the  constitution  of  inorganic  compounds,  we 
will  conclude  by  referring  briefly  to  the  more  successful  application 
of  his  theory  having  reference  to  the  structure  of  the  metalammine 
compounds.  The  metal  in  these  compounds  is  represented  as 
directly  linked  to  four  or  more,  commonly  to  six,  atoms  or  groups 
(NH3,  NO2,  H20,  Cl,  &c.).  This  number  is  called  the  co-ordinate 


VALENCY  ISOMERISM  93 

number,  and  is  a  fundamental  property  of  the  atom.  The  elements 
or  groups  which  are  directly  attached  to  it,  either  by  principal  or 
auxiliary  valencies,  occupy  what  has  been  termed  the  first  zone  and 
do  not  undergo  ionisation. 

Cl  N02 

Cl\  |     xNH3  N02v    |  /NH3 

\  T\l/  A* 


N02 
Cl  N02 

All  those  compounds  in  which  the  maximum  co-ordinate  number 
is  reached  are  called  co-ordinately  saturated.  In  most  cases  the 
co-ordinate  number  is  6,  but  in  some  cases,  as,  for  example,  that  of 
carbon,  the  co-ordinate  number  is  equal  to  the  number  of  principal 
valencies,  namely  4,  and  this  is  true  of  the  other  elements  in  the 
same  periodic  group.  The  neighbouring  more  positive  element 
boron  and  more  negative  nitrogen,  with  three  principal  valencies, 

have  also  a  maximum  co-ordinate  num- 
ber, 4,  and  form  compounds  HF...BF3 


/, 


andXH...NH3. 


At  an  early  stage  in  the  investigation 
of  these  compounds  it  was  discovered 
that  substances  of  the  above  formulae, 
as  well  as  many  others  with  dissimilar 
//  radicals,  existed  in  isomeric  forms.     In 

//  order  to  explain  this  kind  of  isomerism 

Werner  had  recourse  to  a  space  formula 
FIG-  *•  in  which  the  metal  occupied  the  centre 

of  an  octahedron  and  the  atoms  or  groups 

the  six  solid  angles.  By  this  device,  that  is,  by  a  different  space 
distribution  of  the  six  groups,  isomerism  can  be  readily  explained. 
Four  of  the  groups  will  lie  in  one  plane  and  the  others  in  a  plane 
at  right  angles.  The  isomerism  of  the  two  platinum  compounds  will 
appear  as  follows : 


\ 


In  addition  to  this  first  zone  of  non-ionisable  groups,  there  exists  a 
second  or  ionisable  zone.   For  example,  the  following  series  of  cobalt- 


94  THE  VALENCY  OF  CARBON 

ammines  are  known,  in  which  X  stands  for  an  acid  radical  (CJ,N02,&c.). 
CoX3  +  3NH3  CoX3  +  4NH3  CoX3+5NH3  CoX3  +  6NH3 

In  the  second,  third,  and  fourth  compounds  of  this  series  the  sub- 
stances are  ionised,  and  it  has  been  shown  that  the  number  of  ionisable 
acid  radicals  is  respectively  one,  two,  and  three.  This  is  indicated 
by  placing  the  latter  in  a  second  zone  outside  the  bracket,  thus : 

r  X3  i     r  x*  i      r  x  i     r       i 

Co  Co  X  Co  X2         Co(NH3)6  X3 

L    (NH3)J  L    (NH3)J  L    (NHjJ  L  J 

The  outer  zone  is  not  restricted  to  radicals  ;  for  with  an  accumulation 
of  acid  radicals  in  the  inner  zone,  the  outer  zone  may  be  occupied  by 
metallic  atoms,  forming  ionisable  salts.  Examples  of  this  type  are 
potassium  chloroplatinate,  potassium  cobaltinitrite,  and  potassium 
ferro-  and  ferricyanides. 

[PtOlJK,         [Co(N02)6]K3         [Fe(CN)6]K4          [Fe(CN)6]K3 

Potassium  Potassium  Potassium  Potassium 

chloroplatinate.          cobaltinitrite.  ferrocyanide.  ferricyanide. 

Briggs1  has  made  the  interesting  observation  that  space  isomerism 
may  also  be  produced  by  members  of  the  outer  zone,  and  has  prepared 
a  second  modification  of  a  series  of  metallic  ferro  cyanides.  Locke 
and  Edwards  2  have  also  prepared  isomeric  ferricyanides.  The 
existence  of  these  isomers  is  explained  by  a  different  distribution  of 
the  metallic  atoms  among  the  acid  radicals  after  the  manner  of  the 
isomeric  groupings  in  the  first  zone. 


CN 
1 


CN  K 
K-CN  ;  -  -  -CN  R 


I 


y     '*«  / 

CN-K  CNT—  -  1  -  XN 


Clf 


A  further  remarkable  discovery  of  isomerism  among  this  class  of 
substances  has  recently  been  made  by  Werner,3  who  has  succeeded 
in  resolving  asymmetric  compounds  into  their  optically  active  com- 
ponents. Werner  found  at  an  early  stage  in  his  researches  that 

1  Trans.  CJiem.  Soc.,  1911,  99,  1019. 

2  Amer.  Chem.  J.,  1898,   21,  198. 

s  Ber.,  1911,  44,  1887,  2445,  3132,  3272. 


VALENCY  ISOMERISM  95 

NH3  could  be  substituted  by  other  bases  or  organic  amines,  such  as 
pyiidine  and  ethylene  diamine  (NHJCH-j .  CH^NH^,  the  latter 
taking  the  place  of  two  molecules  of  ammonia.  The  formula  for 
ethylene  diamine  may  be  abbreviated  by  using  the  symbol  en.  A 
compound  of  the  formula 

[en2l 
CoNH3  Cla 
Cl'J 

contains  an  asymmetric  inner  zone  and  may  therefore  exist  in 
enantiomorphous  forms. 


e^\] 


The  inactive  preparation  has  been  resolved  by  fractional  crystallisation 
of  the  d-bromocamphor  sulphonates  and  then  converting  them  into 
bromides  (see  Part  II,  p.  304).  The  enantiomorphous  bromides  showed 
a  rotation  of  [a]  =  +  43°,  and  similar  results  were  obtained  with 
other  derivatives  of  cobalt,  as  well  as  with  asymmetric  chromium 
compounds. 

Werner's  co-ordination  theory  is  opposed  by  Friend l  on  the  ground 
that  the  ionized  atoms  are  so  vaguely  disposed  as  to  have  no  definite 
place  or  definite  valency  in  the  compound,  whilst  the  metallic  atom 
has  a  valency  (of  six  in  the  case  of  cobalt)  which  is  contradicted  in 
most  of  its  simpler  compounds.  Furthermore,  the  negative  atoms  or 
groups  directly  attached  to  the  metallic  atom  are  supposed  to  lose 
their  property  of  ionization,  a  fact  which  again  is  contrary  to  ex- 
perience, at  least  in  the  simpler  compounds.  To  overcome  these 
difficulties  Friend  has  had  recourse  to  the  common  valency  values  of 
the  atoms,  and  regards  cobalt  and  platinum  in  the  metalammines  as 
being  directly  united  to  the  negative  atoms,  whilst  the  ammonia  groups 
float  in  a  ring  or  shell  composed  of  linked  nitrogen  or  other  non- 
ionized  atoms  round  the  central  metallic  atom.  Thus  cobalt  hexam- 
mine  trichloride  and  cobalt  chloropentammine  dichloride  are  repre- 
sented thus: 


1  Trans.  Chem.  Soc.,  1916,  109,  715. 


96 


THE  VALENCY  OF  CARBON 


H3N 


NH 


[Co(NH3)G]Cl 


Cl 

[Co(NH,)5Cl]CL 


The  isomeric  a-  and  /?-ferrocyanides  of  Briggs  and  the  a-  and  /?-ferri- 
cyanides  of  Locke  and  Edwards,  referred  to  on  p.  94,  are  explained 
by  supposing  the  central  iron  atom  to  be  united  in  the  ortho,  meta, 
and  para  positions  to  the  nitrogen  atoms  of  the  six  cyanogen 
groups  of  the  ring.  There  would  thus  be  three  isomers,  but  as  the 
ortho  compound  is  assumed  to  represent  the  double  salts  4  KCN, 
Fe(CN)2  and  3  KCN,  Fe(CN)3,  the  meta  and  para  arrangement  are 
reserved  for  the  a-  and  /2-isomers. 

There  are  undoubtedly  difficulties  connected  with  this  theory,  and 
Friend's  views  have  not  passed  unchallenged.  l  The  floating  ring  is 
not  less  vague  than  Werner's  ionized  groups,  the  optically  active 
metalammine  compounds  remain  unexplained,  and  the  ring  chlorine 
atom  in  the  second  of  the  above  formulae  is  furnished  with  the 
unusual  valency  of  three. 

Electrochemical  Theories  of  Valency.  The  application  of  elec- 
tricity to  the  explanation  of  affinity  and  later  of  valency  originated 
in  the  first  instance  in  the  process  of  electrolysis,  which  gave  birth 
to  the  electrochemical  theories  of  Davy  and  Berzelius  (p.  6). 
Those  views  have  in  recent  years  taken  a  more  concrete  and  quanti- 
tative form  by  the  discovery  of  two  correlated  phenomena,  the  first 
being,  that  the  amount  of  electricity  carried  by  the  ion  on  electro- 
lysis is  constant  for  each  unit  of  valency,  and  the  second,  that  it  is 
precisely  this  amount  which  in  the  form  of  the  cathode  ray  is  con- 
veyed by  the  negative  corpuscle  or  electron.  The  electron  may 
therefore  be  regarded  as  the  unit  of  negative  electricity,  the  mass  of 
which  has  been  estimated  at  about  YTO^  °f  that  °^  the  hydrogen 
atom.  The  results  of  electrolysis  led  Helmholtz,2  as  far  back  as 
1881,  to  connect  unit  electrical  charge  with  unit  of  valency,  a  view 
which  he  expounded  in  his  celebrated  Faraday  lecture  in  the  follow- 


1  Turner,  Trans.  Chem.Soc.,  1916,  109,  1130. 

2  Trans.  Chem.  Soc.,  1881,  39,  302. 


ELECTKOCHEHICAL  THEORIES  OF  VALENCY        97 

ing  words  :  '  If  we  conclude  from  the  facts  that  every  unit  of  affinity 
is  charged  with  one  equivalent  either  of  positive  or  negative  electricity, 
they  can  form  compounds,  being  electrically  neutral,  only  if  every 
unit  charged  positively  unites  under  the  influence  of  a  mighty 
electric  attraction  with  another  unit  charged  negatively.  You  see 
that  this  ought  to  produce  compounds  in  which  every  unit  of  affinity 
of  every  atom  is  connected  with  one  and  only  one  other  unit  of 
another  atom.  This,  as  you  will  see  immediately,  is  the  modern 
chemical  theory  of  quantivalence,  comprising  all  the  saturated  com- 
pounds. The  fact  that  even  elementary  substances  with  few  excep- 
tions have  molecules  composed  of  two  atoms  makes  it  probable  that 
even  in  these  cases  electric  neutralisation  is  produced  by  the  com- 
bination of  two  atoms,  each  charged  with  its  full  electric  equivalent 
not  by  neutralisation  of  every  single  unit  of  affinity.' 

The  Electronic  Theory  of  Valency.  Sir  J.  J.  Thomson's  dis- 
covery of  the  electron  and  Rutherford's  interpretation  of  the  break  up 
of  the  radioactive  elements  has  thrown  a  new  light  on  the  structure 
of  the  atom  and  many  of  its  chemical  and  physical  properties.  From 
observations  on  the  small  proportion  of  a-particles  which  are 
deflected  in  their  passage  through  matter,  Rutherford  concludes 
that  almost  the  whole  mass  of  the  atom  is  concentrated  on  a  positively 
charged  nucleus  which  is  of  minute  dimensions  compared  with  that 
occupied  by  the  atom.1  This  nucleus,  which  is  also  associated  with 
negatively  charged  electrons,  is  further  surrounded  by  outer  rings  of 
electrons.  The  magnitude  of  the  positive  charge  in  excess  of  the 
negative  charge  of  the  electrons  attached  to  the  central  nucleus  is 
probably  represented  by  the  atomic  number?  which,  with  the  excep- 
tion of  hydrogen,  is  about  half  the  atomic  weight.3 

The  number  of  negative  electrons  which  neutralize  the  excess 
charge  of  the  positive  nucleus  is,  therefore,  proportional  to  the  atomic 
weight.  On  the  basis  of  this  conception  of  the  atom  and  by  the  aid 
of  the  quantum  principle,  Bohr 4  has  succeeded  in  accounting  for  the 
numerous  line  spectra  of  both  hydrogen  and  helium.  Hydrogen,  it 
appears,  contains  one  positive  charge  and  one  detachable  electron. 
In  the  disintegration  of  the  radioactive  atom,  which  is  accompanied 

1  Phil.  Mag.,  1911,  21,  669;  1914,  27,  323,  488. 

3  Van  den  Broek,  Nature,  1913,  93,  373,  476. 

5  The  atomic  number  represents  the  numerical  order  of  the  elements  as  deter- 
mined by  the  characteristic  lines  of  the  X-ray  spectrum.  This  spectrum  is 
obtained  by  photographing  the  X-rays  given  by  the  element  when  bombarded 
by  the  cathode  stream  in  an  X-ray  bulb,  and  has  been  accurately  mapped  by 
Moseley  (Phil.  Mag.,  1913,  26,  1024)  for  thirty  elements. 

*  Phil.  Mag.,  1913,  26,  17  476;  1914,  27,  506. 

FT.  I  H 


98  THE  VALENCY  OF  CARBON 

by  the  expulsion  of  a-particles  (helium  atoms)  or  /^-particles  (electrons), 
or  both,  it  is  probable  that  the  latter  emanate  from  the  central  nucleus, 
which  will,  therefore,  consist  of  helium  atoms  and  attached  electrons. 
Thus,  the  loss  of  one  a-particle  means  the  loss  of  two  positive  charges 
or  two  places  in  the  atomic  number. 

Thomson's  Theory.  Thomson  describes  the  structure  of  the 
atom  as  follows l :  '  We  find  that  in  a  symmetrical  atom  only  a  limited 
number  of  such  electrons  can  be  in  equilibrium  when  arranged  on  a 
single  spherical  surface  concentric  with  the  atom.  The  actual 
number  which  can  be  arranged  in  this  way  depends  on  the  distribu- 
tion of  positive  electricity  in  the  inside  of  the  atom.  When  the 
number  of  electrons  exceeds  this  critical  number,  the  electrons  break 
up  into  two  or  more  groups  arranged  in  a  series  of  concentric  shells. 
This  leads  us  to  the  view  that  the  electrons  in  an  atom  are  divided 
up  into  a  series  of  spherical  layers,  like  the  coatings  of  an  onion, 
separated  from  each  other  by  finite  distances,  the  number  of  such 
layers  depending  upon  the  number  of  electrons  in  the  atom  and  thus 
upon  its  atomic  weight.  The  electrons  in  the  outside  layer  will  be 
held  in  their  places  less  firmly  than  those  in  the  inner  layers  ;  they  are 
more  mobile,  and  will  arrange  themselves  more  easily  under  the 
forces  exerted  upon  them  by  other  atoms.'  The  existence  of  these 
layers  has  been  proved  by  subjecting  the  elememts  to  bombardment 
by  cathode  rays.  Under  this  treatment  each  element  gives  out  a 
special  kind  of  Rontgen  ray.2  The  speed  of  the  slowest  cathode 
particle  which  could  excite  these  rays  is  proportional  to  the  atomic 
weight,  and  the  frequency  is  proportional  to  the  square  of  the  atomic 
number,  which  is  roughly  that  of  the  atomic  weight.3  These  rays  are 
assumed  to  arise  from  similar  parts,  that  is,  from  the  innermost  ring 
of  electrons. 

On  the  other  hand  the  forces  which  one  atom  exerts  on  another 
will  depend  mainly  on  the  outer  belt  of  the  more  mobile  electrons. 
Thus,  the  increase  of  number  in  the  inner  rings  renders  the  outer 
ring  more  or  less  stable :  in  other  words,  the  outer  ring  may  tend  to 
lose  or  gain  electrons,  thus  converting  the  atom  into  an  electro- 
positive or  electronegative  element,  and  the  number  of  electrons 
which  it  tends  to  gain  or  lose  will  determine  the  valency.  If  these 
properties  are  recurrent  after  the  addition  of  a  certain  number  of 
electrons,  the  atoms  will  exhibit  periodic  changes  in  conformity  with 

1  The  Atomic  Theory,  by  Sir  J.  J.  Thomson,  Clarendon  Press,  1914. 

2  Whiddington,  Proc.  Camb.  Phito.  Soc.,  1910. 

3  Moseley,  Phil.  Mag.,  1913,  26,  1024. 


THOMSON'S  THEORY  99 

the  periodic  law.  Thus,  the  number  of  mobile  electrons  in  group  O 
is  nil,  that  of  the  alkali  metals  is  one,  and  so  forth.  When  the 
number  reaches  eight  the  ring  becomes  stable  and  the  electrons  no 
longer  mobile.  The  outer  belt  of  electrons  is  also  responsible  for 
certain  optical  properties,  such  as  left-activity  and  dispersive  power, 
and  such  physical  phenomena  as  surface  tension,  cohesion,  intrinsic 
pressure,  viscosity,  ionizing  power,  in  fact,  by  far  the  most  important 
properties  of  the  atom. 

Thomson1  regards  valency  as  a  tube  of  force  emanating  from  a 
valency  electron  and  either  ending  on  the  positive  charge  within  the 
atom,  when  they  retain  their  mobility,  or  on  that  of  another  atom, 
when  they  become  fixed.  When  all  are  fixed  in  this  way,  the  atom 
is  saturated.  It  follows,  therefore,  that  in  a  molecule,  say  of  hydrogen, 
for  every  tube  of  force  sent  out  from  the  electron  ot  one  atom  the 
latter  must  be  the  recipient  of  a  second  tube  of  force  sent  out  from 
the  second  atom.  Thus,  the  atom  of  hydrogen  must  be  divalent  and 
possess  one  positive  and  one  negative  valency  which  Thomson 
represents  by  arrows  : 

H  ^±  H 

Further,  chemical  compounds  are  divided  into  two  classes,  those 
which  have  undergone  intramolecular  ionization,  that  is,  have  lost  or 
gained  electrons  in  the  process,  or  ionic  molecules,  and  those  which 
have  not. 

Thomson's  views  have  given  rise  to  various  interpretations  of  the 
electronic  theory  of  valency. 

Ramsay,2  like  Stark,  assumes  that  the  electron  is  the  binding  force 
between  the  atoms  in  a  molecule.  He  regards  eight  as  the  total 
number  of  electrons  that  an  atom  can  hold.  Thus,  in  ammonia  the 
nitrogen  atom  which  already  possesses  five  electrons  receives  three 
from  the  hydrogen  atoms,  making  a  total  of  eight.  No  additional 
electrons  can  now  be  added  unless  one  is  removed,  so  that  the  ninth 
valency  in  ammonium  chloride  is  negative.  This  view  of  Ramsay's 
on  the  concurrent  addition  and  removal  of  an  electron  finds  ex- 
pression in  Friend's  residual  or  latent  valencies*  the  neutral  affinities 
of  Spiegel,4  and  the  electrical  double  valencies  of  Arrhenius.5  They 
serve,  among  other  things,  to  bind  the  atoms  in  the  molecule  of  an 
element  or  two  electropositive  elements  such  as  potassium  hydride, 
whilst  the  ordinary  valencies  are  utilized  for  linking  electropositive 
and  negative  atoms.6 

1  Phil.  Mag.,  1914,  27,  757.  2  Trans.  Chem.  Soc.,  1908,  93,  778. 

3  Trans.  Chem.  Soc.,  1908,  93,  260.  4  Zeit.  anorg.  Chem.,  1902,  29,  365. 

5  Theorien  der  Chemie,  Leipzig,  1906. 

6  The  electronic  theory  of  valency  is  responsible  for  a  number  of  highly  sug- 
gestive interpretations   of  such  processes  as  the  affinity  constants  of  organic 

H   2 


100  THE  VALENCY  OF  CAKBON 

Stark's  Theory.1  According  to  Stark  there  are  two  kinds  of 
electrons,  fixed  and  movable.  The  fixed  electrons  are  disposed 
within  the  positively  charged  sphere  constituting  the  atom,  the 
movable  electrons  lie  outside  the  atom  and  at  some  little  distance 
from  it  and  are  attached  to  it  by  lines  of  force.  The  movable  electrons 
have  been  termed  valency  electrons.  It  is  by  means  of  these  electrons 
that  combination  is  effected  between  similar  atoms  to  form  molecules 
and  between  dissimilar  atoms  to  form  compounds.  Lines  of  force 
pass  out  from  the  electrons  to  other  atoms  with  a  loss  of  potential 
energy.  According  to  the  number  of  these  lines,  attachment  is 
weaker  or  stronger.  Thus,  atoms  do  not  combine  directly,  but  in- 
directly by  virtue  of  their  mutual  attraction  to  the  electron.  A  single 
bond  will  correspond  to  a  union  by  means  of  one  electron,  a  double 
bond  by  that  of  two  electrons,  a  treble  bond  by  three,  and  a  free 
bond  will  be  represented  by  an  unattached  electron.  The  existence 
of  stereoisomerism  is  readily  explained  on  the  assumption  that  the 
lines  of  force  of  the  valency  electrons  are  confined  to  definite  areas 
on  the  atom.  What  is  the  number  and  distribution  of  the  valency 
electrons  ?  Whilst  positive  valency  can  be  determined  by  the  number 
of  valency  electrons  that  an  atom  can  lose  on  ionisation,  the  negative 
valency  may  be  derived  from  the  fact  pointed  out  by  Abegg  (see 
below)  that  the  sum  of  the  maximum  positive  and  negative  valencies 
of  any  atom  is  eight.  Thus,  carbon  has  a  valency  of  -  4  in  CH4  and 
+  4  in  CC14,  phosphorus  of  -3  in  PH3  and  +5  in  PC15,  iodine  of 
-  1  in  HI  and  +  7  in  I2O7. 

It  appears,  therefore,  that  the  greatest  number  of  valency  electrons 
which  an  atom  can  hold  is  eight.  Driide,  on  the  other  hand? 
estimates  the  number  of  valency  electrons  from  the  positive  valency 
of  the  atom,  from  which  it  follows  that  the  smaller  the  negative 
valency,  the  larger  the  number  of  valency  electrons. 

Stark  regards  the  difference  between  electropositive  and  negative 
elements  as  due  to  the  greater  or  smaller  positive  charge  on  the  atom. 
An  electronegative  atom,  such  as  chlorine,  will  be  one  with  a  large 
positive  charge  and  therefore  able  to  retain  a  number  of  electrons,  or 
attract  others  from  electropositive  atoms.  An  electropositive  element, 
such  as  hydrogen,  will,  on  the  other  hand,  have  a  small  positive 
charge,  which  requires  few  electrons  to  neutralize  it,  and  the  latter 
will  be  attracted  to  electronegative  atoms  of  large  positive  charge. 

acids,  substitution  in  benzene,  &c.,  in  numerous  papers  by  H.  S.  Fry,  K.  G.  Falk, 
and  W.  A.  Noyes,  which  have  appeared  since  1910  in  the  Journal  of  the  American 
Chemical  Society,  and  which  being  of  rather  special  than  general  application,  and 
to  which  full  justice  cannot  be  done  within  necessary  limits  of  space,  must  be 
left  to  the  reader  for  reference. 

1  Prinzipien  der  Atomdynamik.     J.  Stark.     Hirzel,  Leipzig,  1910. 


ST ARK'S  THEORY  101 


The  reactivity  of  both  kinds  of  atoms  will  be  due  to  the  ease  with 
which  they  attract  or  repel  electrons. 

An  atom,  such  as  carbon,  which  combines  with  both  electropositive 
and  negative  elements,  is  assumed  to  possess  four  electrons,  with 
which  it  is  able  to  bind  four  equivalent  electronegative  atoms ;  but 
as  the  lines  of  force  of  the  electrons  occupy  a  restricted  area  on  the 
atom,  the  lines  of  force  of  four  electropositive  atoms  may  fall  on 
intermediate  positively  charged  areas.  It  is  not,  however,  clear 
why  the  two  kinds  of  valency  should  not  function  at  the  same  time, 
a  condition  which,  at  least  in  the  case  of  carbon,  is  unknown.  In 
addition  to  the  property  of  causing  combination,  Stark,  like  Thomson, 
holds  that  the  valency  electrons  are  probably  responsible  for 
ionisation  and  the  phenomenon  of  light  absorption  and  other  optical 
properties  (see  Part  II,  p.  70). 

Thus  the  form  of  the  positive  sphere,  the  number  and  position 
of  the  electrons,  and  the  distribution  of  the  lines  of  force  determine 
the  character  of  the  atom,  that  is,  its  affinity,  valency,  &c.  It  is  by 
the  lines  of  force  emanating  from  the  valency  electrons  that  affinity 
is  manifested  and  atoms  are  bound  together  in  a  molecule. 

In  unsaturated  compounds  it  is  assumed  that  there  is  a  certain 
amount  of  residual  affinity,  that  is,  valency  electrons  whose  lines 
of  force  are  turned  back  and  end  on  the  positive  spheres  of  the 
unsaturated  atoms.  Addition  produces  a  fusion  of  the  lines  of  force 
of  the  unsaturated  atoms  with  those  of  the  added  atoms  and  conse- 
quent degradation  of  energy  of  the  system.  The  unlocking  or 
opening  of  these  lines  of  force  may  be  produced  by  adding  energy 
to  the  system  in  various  forms,  heat,  light,  or  the  action  of  the 
solvent,  &C.1  This  change  in  the  energy  content  affecting  the 
electrons  in  the  molecule  is  manifested  by  the  absorption  of  light 
or  by  the  associated  phenomena  of  fluorescence,  phosphorescence, 
or  photochemical  action,  referred  to  in  Part  II,  p.  130  et  seq. 

Theory  of  Abegg  and  Bodlander.2  A  brief  reference  has  already 
been  made  to  this  theory  and  the  meaning  which  is  attached  to  the 
term  normal  and  contra-valencies  (p.  58).  The  normal  valencies  are 
the  stronger  and  are  electropositive  for  metals  and  electronegative 
for  non-metals.  Their  strength  is  affected  by  combination,  which 
falls  off  as  saturation  proceeds.  The  activity  of  the  contravalencies 
increases  with  increase  in  the  negative  character  of  the  element  and 

1  Baly,  Zeit.  /.  Elekirochemie,  1911,  17,  211  :  Trans.  Chem.  Soc.,  1912,  101,  1469, 
1475. 
»  Zeit.  anorg.  Chem.,  1899,  20,  453 ;  1904,  39,  330. 


102  ;  :  HjSEr  ^ALESjET  OF  CARBON 

also  with  its  atomic  weight.  This  explains  the  existence  of  a  stable 
oxide  of  iodine  but  not  of  fluorine.  The  activity  of  the  contra- 
valencies  among  negative  elements  also  determines  the  formation  of 
di-  and  poly-atomic  molecules.  Being  latent  in  the  metal,  they  possess 
monatomic  molecules.  The  existence  of  latent  contra  valencies  explains 
the  formation  of  molecular  compounds  whose  component  molecules 
are  similar.  For  when  uncombined  one  component  should  contain 
an  element  belonging  to  the  higher  groups  of  the  periodic  system, 
and  this  is  found  to  be  the  case.  Compounds  such  as  H20,  N02,  HF, 
A1C13,  &c.,  and  organic  hydroxy-compounds,  oximes,  and  aldehydes 
enter  into  molecular  compounds.  The  double  fluorides  and  chlorides, 
water,  and  alcohol  of  crystallisation  are  examples.  The  same  reasoning 
accounts  for  ordinary  molecular  compounds  such  as  (CH3)2O  .  HC1, 
NH3.  HC1.  In  the  latter  case  the  formula  will  be  represented  thus  : 


H+  -        ~ 

but  it  is  improbable  for  reasons  already  given  (p.  58)  that  the  fourth 
hydrogen  atom  is  combined  differently  from  the  other  three. 
Solutions  where  combination  of  solute  and  solvent  is  indicated  by 
thermal  and  other  changes  are  placed  in  the  category  of  molecular 
compounds.  These  changes  are  most  marked  when  substances 
contain  elements  of  high  but  unsaturated  valency. 

In  electrolytic  solutions  the  following  equilibria  may  occur  : 

Ion  +  ion          ^±  Undissociated  molecules. 
Ion  +  solvent  ^±  Compound  of  ion  +  solvent. 
Undissociated  molecules  +  solvent  ^±  Compound  of  the  same. 

Feebly  dissociating  solvents  are  those  which  have  no  great 
tendency  to  combine  with  ions.  If  the  tendency  to  ionisation  is 
well  developed,  the  affinity  of  the  Undissociated  substance  for  the 
solvent  is  unimportant,  as  the  non-ionised  substance  will  not  reach 
a  high  concentration  compared  with  the  ions.  The  case  is  represented 
by  solutions  of  strong  electrolytes  whose  solubility  is  determined 
by  the  affinity  of  ions  for  the  solvent,  and  is  therefore  great  in  water, 
compared  with  the  solubility  in  fully  dissociated  media.  Sulphur 
dioxide,  for  example,  is  found  to  combine  with  those  substances 
which  undergo  ionisation  in  the  liquid. 

Briggs'  Theory.  Briggs1  has  applied  Abegg's  theory  in  order 
to  explain  the  structure  of  the  metalammine  compounds.  The 

1  Trans.  Chem.  Soc.,  1908,  93,  1564;  1917,  111,  253. 


BRIGGS'  THEORY  103 

radicals  do  not  form  two  zones  as  Werner  supposes,  but  are  all 
directly  attached  to  the  metallic  atom  by  virtue  of  their  positive 
and  negative  affinities,  with  which  each  atom  is  provided.  For 
example,  the  platinum  atom  is  capable  of  combining  with  six  positive 
affinities  and  four  negative  affinities.  By  its  positive  affinities  it  can 
attach  the  negative  affinities  of  four  atoms  of  chlorine,  and  by  its 
negative  affinities  it  can  attach  the  positive  affinities  of  six  molecules 
of  ammonia.  Ammonia  has  only  one  available  positive  affinity,  since 
its  other  positive  and  negative  affinities  are  saturated  by  the  positive 
and  negative  affinities  of  hydrogen. 

H 


It 

H 

Chlorine  has  one  positive  and  one  negative  affinity.  The  three 
compounds  (Pt  4NH3C12)C12,  (Pt  3NH3C13)C1,  and  (Pt  2NH3C15)  may 
be  represented  by  the  following  formulae,  in  which  the  free  affinities 
are  indicated  by  dotted  arrows  and  the  combined  positive  and  negative 
by  arrows  pointing  in  reverse  directions. 

Nf3  NH3  NH3 

«~C1«-   ^  i  1 

^         — >  pi  '"  — >  pi         pi  — *•        — >  pi 

*   -pf   < —  ^/1  "WTT    *.   "Pf   < —  •* —  "Pf   < — 

^     -L   t    ^    pi  i^J.a3        ^    A   t     >   pi  pi    ^.    J.  b    ^,   pi 

— >  <       Ol  pi^ >  ^ vyl  v^l  ^ <       C»l 

*-<5l*-  -  t  t 

Nk  NH'  NH= 

I.  II.  III. 

The  chlorine  atoms  with  free  affinities  are  those  which  undergo 
ionisation.  Thus,  in  I  two  atoms  of  chlorine  and  in  II  one  atom  of 
chlorine  are  ionised,  whereas  III  is  electrically  neutral.  The  same 
idea  has  been  applied  to  formulating  K2PtCl6, 

Cl  <-  K 

I 
Cl  «±  pt  «±  Cl 

01  ^  K  <  - 

in  which  the  two  metal  atoms  attached  to  the  free  affinities  of  the 
two  chlorine  atoms  undergo   ionisation.     Briggs  has  also  applied 


104          THE  VALENCY  OF  CARBON 

Abegg's  solution  equilibria,  referred  to  above,  in  order  to  show  that 
there  will  be  less  tendency  on  the  part  of  the  chlorine  atoms  towards 
ionisation  by  reason  of  the  residual  affinity  of  the  water  molecules 
when  attached  by  two  kinds  of  affinity  than  by  one. 
.  This  theory  has  undergone  a  further  development  in  the  following 
way  :  It  has  been  stated  (p.  99)  that  J.  J.  Thomson  recognizes  two 
types  of  chemical  combination  producing  ionic  and  non-ionic  mole- 
cules. Bray  and  Branch  l  and  Gr.  N.  Lewis  2  draw  a  similar  distinc- 
tion between  polar  and  non-polar  compounds.  In  the  polar  compounds 
(Thomson's  ionic  molecules)  a  transfer  of  electrons  from  one  atom  to 
another  has  taken  place.  In  the  non-polar  compounds  electrons  have 
not  been  transferred,  and  the  atoms  are  held  together  by  equal  and 
opposite  tubes  of  force  passing  from  the  electrons  in  one  atom  to  the 
positive  nucleus  of  the  other.  Moreover,  all  gradations  between  a 
completely  polar  and  a  completely  non-polar  molecule  are  to  be 
expected.  In  addition  to  the  dual  affinity  of  the  atoms  as  exhibited 
by  a  tendency  to  both  gain  and  lose  electrons,  Briggs  distinguishes 
between  primary  and  secondary  affinity,  the  latter,  which  is  opposite 
in  sign  to  the  former,  only  coming  into  action  when  the  primary 
affinity  has  been  saturated.  In  the  strong  electrolytes  (polar  com- 
pounds), such  as  potassium  chloride,  the  atoms  are  united  by  primary 
affinity  only,  the  secondary  affinity  (dotted  arrow)  being  unsaturated, 
as  represented  by  the  formula  : 

...»  K  ->  Cl  -> 

In  the  non-electrolytes  (non-polar  compounds),  such   as  methane, 
the  atoms  are  united  by  both  primary  and  secondary  affinity. 

II 


U 

Methane. 

Now,  copper  is  incapable  of  direct  combination  with  ammonia 
molecules  to  give  compounds  of  the  type  Cu.  #NH3.  Cuprous 
chloride,  however,  can  combine  with  a  maximum  of  three  molecules 
of  ammonia  to  give  (Cu,3NH3)Cl,3  and  cupric  chloride  with  six 
molecules  of  ammonia  (Cu,  6NH3)C12.  That  is  to  say,  the  ammonia 
molecules  are  united  to  the  copper  by  the  saturation  of  the  free 

1  .7.  Amer.  Chem.  Soc.,  1913,  35,  1443. 
8  J.  Amer.  Chem.  Soc.,  1913,  35,  1448. 
8  Lloyd,  J.  Phys.  Chem.,  1908,  12,  393. 


BRIGGS'  THEORY  105 

positive  affinity  of  the  nitrogen  in  ammonia  «— NH3  by  the  negative 
affinity  of  the  copper  in  the  two  salts.  But  since  the  copper  atom 
alone  cannot  combine  directly  with  ammonia,  it  evidently  does 
not  possess  negative  affinity.  Cuprous  salts,  however,  can  combine 
with  ammonia,  and  cupric  salts  with  a  still  larger  quantity ;  hence 
the  copper  atom,  on  losing  an  electron,  develops  negative  affinity, 
and  with  a  loss  of  two  the  negative  affinity  becomes  more  marked. 
It  therefore  follows  that  the  negative  affinity  of  the  copper  is  a 
secondary  phenomenon  which  only  appears  when  the  primary  affinity 
has  come  into  action. 

In  this  way  the  relative  stability  of  the  metalammine  salts,  as  de- 
termined by  Ephraim1  from  the  temperature  required  to  produce 
a  constant  dissociation  pressure,  can  be  readily  explained. 

Similar  views  have  been  applied  to  acids  and  bases.  The  strongest 
and  weakest  acids  may  be  written  : 

~»  H  ->  X  ...»  H  ±^  X 

Strong  acid.  Weak  acid. 

If  the  secondary  affinity  of  X  in  a  weak  acid  is  saturated  by 
combination  with  a  molecule  M  to  give  a  complex  acid,  this  complex 
acid  will  have  the  formula 

-»  H  -»  XM 

and  since  the  secondary  affinity  of  X  is  now  saturated,  the  secondary 
affinity  of  the  hydrogen  will  be  free,  and  its  tendency  to  undergo 
electrolytic  dissociation  thereby  increased.  Whereas  hydrocyanic 
acid  is  a  very  weak  acid,  hydrogen  ferrocyanide,  ferricyanide,  and 
cobalticyanide  are  all  strong  acids.  The  same  principles  hold  in  the 
case  of  bases,  the  formulae  for  which  fall  between  the  types 

...>  R  _»  OH  -»     and    R  ±^  OH 

Strong  base.  Weak  base. 

When  the  secondary  affinity  of  R  in  the  weak  base  is  saturated  by 
combination  with  a  molecule  A,  a  complex  and  strong  base  of  the 
formula  (RA)  — >  OH  is  obtained,  examples  of  which  are  afforded  by 
the  strongly  alkaline  compounds  of  ammonia  with  weakly  basic 
metallic  hydroxides.  Moreover,  two  or  more  molecules  of  the  same 
compound  may  be  united  by  secondary  affinity  and  give  rise  to 
polymerisation. 

1  Ber.,  1912,  45,  1322 ;  1913,  16,  3103  ;  1914,  47,  1828. 


106 


REFERENCES. 

The  TJieory  of  Valency,  by  J.  N.  Friend.  Second  edition.  Text-books  of  Physical 
Chemistry.  Longmans,  1915. 

Outlines  of  Chemisfry,  Chapter  IX,  by  H.  J.  H.  Fenton.  Cambridge  Univ.  Press, 
1910. 

Neuere  Anschauungen  aufdem  Gebiete  der  anorganischen  Chemie,  2nd  ed.  by  A.  Werner. 
Vieweg,  Brunswick,  1909 ;  or  New  Ideas  of  Inorganic  Chemistry,  by  the  same, 
translated  by  E.  P.  Hedley.  Longmans,  1911. 

Modern  Electrical  TJieory,  by  N.  R.  Campbell.  Cambridge  Univ.  Press,  2nd 
edition,  1913. 

The  Atomic  Theory,  by  Sir  J.  J.  Thomson.     Clarendon  Press,  Oxford,  1914. 


CHAPTER  III 

THE  NATURE  OF  ORGANIC  REACTIONS 

IN  the  preceding  chapter  we  have  discussed  the  valency  of  carbon 
and  the  views  which  have  heen  put  forward  to  explain  the  pheno- 
menon. We  have  now  to  inquire  into  the  causes  which  bring 
about  the  interaction  of  two  substances. 

Valency  and  Affinity.  The  first  question  which  naturally 
suggests  itself  is  what  relation  exists  between  valency  and  chemical 
affinity ;  does  the  quadrivalency  of  carbon,  compared,  say,  with 
the  uni valency  of  chlorine,  imply  a  correspondingly  higher  chemical 
affinity?  Before  answering  this  question  it  may  be  well  to 
consider  briefly  the  nature  of  chemical  affinity,  or  the  force  which 
binds  the  elements  together.  This  has  already  been  touched  upon 
in  the  previous  chapter.  It  is  generally  assumed  that  opposite 
electrical  properties  of  the  elements  determine  the  readiness  with 
which  they  unite  and  the  stability  of  the  union.  It  is  manifested 
by  the  evolution  of  heat  or  by  the  loss  of  some  other  form  of 
energy.  Thus,  hydrogen  and  chlorine,  representing  a  highly 
electropositive  and  electronegative  element  in  the  electrochemical 
series,  unite  with  loss  of  energy,  and  this  energy  must  be  supplied 
if  it  is  desired  to  break  down  the  union  ;  in  other  words,  the  greater 
the  loss  of  energy,  the  greater  the  stability  of  the  product.  The 
compound  formed  in  this  case,  namely,  hydrogen  chloride,  is  highly 
ionised  in  aqueous  solution.  Exactly  the  same  is  true  of  the 
compound  of  sodium  and  chlorine.  On  the  other  hand,  we  have  the 
phenomenon  of  atoms  of  the  elementary  gases  joining  together  in 
the  form  of  molecules  and  of  still  more  highly  polymerised  forms, 
as,  for  example,  carbon  and  sulphur,  of  such  stability  that  they  are 
only  decomposed  with  difficulty. 

It  is  clear  then  that  chemical  affinity  is  at  times  independent  of 
opposite  electrical  character  unless  we  are  prepared  to  admit,  like 
Abegg  and  Bodlander  and  others  (p.  101),  that  the  atoms  are  furnished 
with  both  positive  and  negative  charges  which  may  be  brought  into 


108  THE  NATURE  OF  ORGANIC  REACTIONS 

action  when  required.  This  view  is,  however,  attended  by  serious 
difficulties,  which  may  be  illustrated  in  the  case  of  carbon.1 

Carbon,  as  already  pointed  out,  occupies  a  unique  position  in  the 
periodic  table.  Its  position  midway  in  the  electrochemical  series 
gives  it  a  neutral  character  which  enables  it  to  enter  into  union  with 
both  electropositive  elements,  such  as  hydrogen,  and  electronegative 
elements  like  chlorine.  It  is  noteworthy  that  although  free  carbon 
can  only  be  induced  to  combine  with  great  difficulty  with  either 
hydrogen  or  chlorine,  the  compounds  formed,  CH4  and  CC14,  are 
not  only  stable  at  moderately  high  temperatures  and  under  the 
action  of  many  reagents,  but  are  not  appreciably  dissociated  in 
solution.  Moreover,  the  elements  linked  to  carbon  retain  something 
of  their  properties  in  the  free  state.  Carbon,  for  instance,  when 
combined  with  hydrogen,  forms  a  strongly  electropositive  methyl 
group,  but  when  joined  to  chlorine  produces  a  strongly  electronegative 
CC13  group.  The  effect  is  seen  on  introducing  the  two  groups  in 
place  of  hydrogen  into  formic  acid,  Acetic  acid,  CH3 .  COOH,  is 
weaker  by  about  one-twelfth  than  formic  acid,  as  proved  by  its 
affinity  constant ;  trichloracetic  acid  has  more  than  5,000  times  the 
strength. 

This  peculiar  character  of  carbon  of  acting  as  a  neutral  atom  to 
which  other  atoms  may  become  attached  without  renouncing  their 
original  properties  has  been  referred  to  by  van 't  Hoff 2  as  inertia 
(Tragheit)  and  by  Michael  as  plasticity.*  It  is  to  this  same  inert 
character  that  van 't  Hoff  attributes  the  slow  reactivity  of  organic  as 
compared  with  inorganic  compounds,  or,  as  we  should  now  say,  the 
smaller  tendency  to  ionisation.4 

But  if  carbon  exerts  little  influence  on  the  character  of  the  atoms 
attached  to  it,  it  preserves  the  property,  which  it  possesses  in  the 
free  state,  of  polymerising,  that  is,  of  combining  with  itself  to  form 
aggregates  of  atoms  and  carbon  chains.  This  again  appears  to  be 
a  peculiarity  of  its  position  in  the  periodic  system  ;  for  the  tendency 
to  polymerise  or  to  form  chains  falls  away  in  the  periodic  groups 
lying  to  the  right  and  left  of  carbon.  Chains  of  three  and  four  atoms 
of  nitrogen  are  known,  but  are  unstable,  and  attempts  to  lengthen 
them  have  met  with  increasing  difficulty,  whilst  in  the  case  of 

1  Some  of  the  ideas  which  are  expressed  hei-e  are  derived  from  tlie  Ansichten 
uber  die  organische  Chemie,  by  J.  H.  van't  Hoff,  2  vols.,  1878  and  1881,  Vieweg, 
Brunswick.  Although  this  classic  is  now  nearly  a  third  of  a  century  old  and 
appeared  at  a  time  when  organic  chemistry  was  undergoing  its  most  rapid 
development,  many  of  the  views  which  find  expression  there  are  still  eminently 
suggestive  and  as  applicable  to  present-day  problems  as  when  they  first  appeared. 

a  Ansichten,  vol.  i,  p.  244.  8  J.  prakt.  Chem.,  1899,  60,  325. 

*  Ansichten,  vol.  i,  p.  286. 


VALENCY  AND  AFFINITY  109 

oxygen  the  peroxides,  peracids,  and  ozonides  readily  and  sometimes 
explosively  break  up  and  lose  oxygen. 

We  may  then  ask  :  is  this  tendency  to  polymerise  which  is 
exhibited  by  free  carbon  in  carbon  chains  effected  by  means  of  the 
opposite  electrical  polarities  of  the  individual  atoms  ?  If  so,  the  end 
atoms  of  a  chain,  like  the  top  and  bottom  discs  of  a  voltaic  pile, 
should  show  opposite  polarities ;  but  there  is  no  evidence  that  this 
is  the  case.  For  if  it  were  so,  the  halogen  atoms  at  the  two  ends 
of  a  carbon  chain  should  possess  different  reactivities,  which  they 
do  not,  otherwise  hexylene  dibromide  and  sodium  should  yield 
dodecylene  dibromide,  C12H24Br2,  whereas  cyclohexane  is  formed.1 

We  may  therefore  conclude  that  the  tendency  to  polymerise,  like 
chemical  affinity,  is  a  function  of  the  atomic  weight  and  is  associated 
with  the  position  of  the  element  in  the  periodic  system  ;  that  increase 
of  valency  up  to  the  central  group  is  not  attended  by  an  increase,  but 
by  a  decrease  in  chemical  energy.2  According  to  van't  Hoff3  it  is 
the  high  valency  combined  with  the  chemical  ineitia  of  carbon 
which  determines  its  union  with  so  many  different  elements,  as  well 
as  with  itself,  and  which  explains  at  the  same  time  the  formation  of 
the  vast  number  of  organic  compounds. 

Types  of  Reactions.  What,  then,  determines  chemical  union  ? 
Before  answering  this  question  we  will  consider  the  different  kinds 
of  organic  reactions.  Van  't  Hoff  *  classifies  them  into  three  types. 
In  the  first,  addition  occurs  between  two  unsaturated  molecules  by 
means  of  one  of  the  double  bonds  without  cleavage  of  either  molecule. 

The  product  has  in  consequence  a  cyclic  structure, 
OC  NH  OC— NH 

+        11  =  II 

HN  C:NH  HN— C:NH 

Cyanic  acid.         Cyanamide.  Carbodiimide. 

In  the  second  type,  addition  occurs  between  an  unsaturated  and 

a  saturated  molecule,  with  cleavage  of  the  saturated  molecule.     The 

additive  compounds,  which  the  olefines  form,  come  under  this  head. 

H2C        Br        CH2Br 

II    +     I      =1 
H2C        Br        CH2Br 

The  third  type  represents  ordinary  substitution  in  which  both 
molecules  are  saturated.5 

1  W.  H.  Perkin,  Ber.,  1894,  27,  216. 

8  Blomstrand,  Chemie  der  Jetzteeit,  1869,  217,  213.      Hinriclisen,  Zeit.  physik. 
am.,  1901,  39,  305. 

3  Atisichten.  vol.  ii,  p.  240.  *  Ansichten,  vol.  i,  p.  8. 

6  There  is  a  fourth  type  in  which  the  molecule  interacts  with  itself,  condenses 


110  THE  NATURE  OF  ORGANIC  REACTIONS 

To  explain  the  union  of  methane  with  chlorine  we  shall  have  to 
assume  one  of  two  things,  either  that  addition  precedes  substitution, 
CH,  +  C12  =  CH4C12 
CH4C12  =  CHoCl-f  HC1 

or  that  each  molecule  under  the  influence  of  the  other  dissociates, 
the  methane  into  methyl  and  hydrogen,  and  molecular  into  atomic 

chlorine. 

CH,     Cl     CH.5C1 

:          +   :     =        + 

H        Cl      HC1 

The  first  view  was  held  by  A.  Kekule,  and  in  a  modified  form 
by  J.  U.  Nef ;  the  second  by  Williamson,  who  gave  expression  to  it 
in  propounding  his  'Theory  of  Etherification '  (1851).  Kekule,  in 
his  Lelir'bucli  (1867),  says :  '  When  two  molecules  react  upon  one 
another,  they  attract  one  another  by  their  affinity  and  unite ;  the 
relation  between  the  affinities  of  the  single  atoms  frequently 
causes  the  atoms,  which  had  previously  belonged  to  different 
molecules,  to  come  into  the  closest  attachment.  On  this  account 
the  atomic  groups  which  were  originally  separated  in  one 
direction,  when  joined  to  the  other  molecule,  separate  in  another 
direction.'  The  process  may  be  represented  by  black  and  white 
spheres,  thus : 

Si     O  *0       a.          . 

+   0"~*"«0^+  *  o 

•O 

This  view  has  been  very  generally  adopted.  Van  't  Hoff 1  has 
pointed  out  that  many  substitution  processes  may  be  most  simply 
explained  by  addition,  and  Michael2  has  accepted  the  same  view, 
which  will  be  more  fully  discussed  later.  It  receives  further  support 
from  the  theory  of  enzyme  action,  according  to  which  enzyme  and 
substrate  unite  before  cleavage  (Part  III,  p.  98),  and  from  Fischer's 
explanation3  of  optical  inversion  (Part  II,  p.  197),  whereby  the 
reagent,  which  causes  it,  is  represented  as  attaching  itself  to  the 
atom  before  forming  an  additive  compound  which  subsequently 
breaks  down  in  a  manner  which  may  or  may  not  cause  a  change  in 
the  spatial  arrangement  of  the  remaining  groups.  The  researches  of 
Schmidlin  and  Lang,4  who  have  been  able  to  prove  the  existence  of 
such  additive  compounds  from  a  study  of  the  melting-point  curves  of 
reacting  compounds,  point  in  the  same  direction.  The  theory  also 

or  polymerises.   All  the  four  types  may  occur  in  the  case  of  a  single  compound 
as  illustrated  by  the  ketenes  (p.  66). 

1  Ansichten,  vol.  i,  pp.  225,  244.  2  J.  prakt.  Chem.,  1883,  37,  486. 

5  Annalen,  1911,  381,  123.  *  Ber.,  1910,  43,  2806;  1912,  45,  899. 


TYPES  OF  REACTIONS  111 

fits  in  with  Werner's  notion  of  residual  affinity  or  auxiliary  valencies. 
In  this  connection  it  is  interesting  to  note  that  Kekule,  who  was 
a  strong  supporter  of  the  theory  of  fixed  valency,  should  have 
originated  an  idea  which  was  directly  opposed  to  it. 

Nef l  considers  that  chemical  reactivity  depends  on  dissociation, 
and  at  the  same  time  on  the  additive  power  of  the  substituting 
molecule,  by  virtue  of  its  residual  valencies. 

CH3— H  +  Cl  =  Cl  =  CH,  H  =  CH,C1  +  HC1 

1       '         I         I 
C1=C1 

Both  these  views  have  been  extended  to  the  synthesis  of  organic 
compounds,  in  which  wide  scope  is  given  to  their  application 
(p.  230). 

There  is  a  fourth  type  of  reaction  in  which  both  reacting  molecules 
are  saturated,  yet  unite  without  cleavage.  Under  this  type  may  be 
included  those  loose  combinations,  commonly  known  as  molecular 
compounds,  represented  by  substances  containing  alcohol,  benzene, 
and  chloroform  of  crystallisation,  those  formed  by  the  union  of 
aromatic  nitro  and  nitroso  compounds 2  with  aromatic  hydrocarbons 
and  amino  compounds,  perbromides  of  the  organic  bases,  and  com- 
pounds such  as  piperidine  and  carbon  tetrabromide,  C5HnN(CBr4).3 
As  already  stated,  such  combinations  find  no  place  in  the  ordinary 
views  of  a  definite  valency  number,  but  are  readily  explained  on 
Werner's  theory. 

Among  the  many  reactions,  drawn  from  one  or  other  of  the 
different  types,  which  might  be  discussed,  we  propose  to  limit 
ourselves  for  the  present  to  those  of  the  unsaturatcd  compounds,  as 
having  been  most  carefully  studied  and  affording  the  most  varied 
and  most  interesting  results. 

Addition.  Reactions  of  Unsatnrated  Compounds.  The  simplest 
case  of  a  reaction  between  molecules  is  one  where  direct  union  occurs. 
The  theory  of  unsaturated  compounds  depends  in  the  first  instance  on 
the  formation  of  what  are  termed  additive  compounds  (p.  113). 
Where  they  are  formed  it  is  possible,  as  a  rule,  to  discover  one  or 
more  elementary  atoms  in  the  original  compound  whose  maximum 
valency  has  not  been  utilized,  and  these  atoms  are  represented  as 
points  of  attachment  for  the  new  molecule  or  molecules.  Thus, 
hydrocarbons  of  the  ethylene  and  acetylene  type  and  their  derivatives, 

1  Annalen,  1891,  266,  59  ;  Journ.  Amer.  Chem.  Soc.,  1904,  26,  1563. 

*  Schraube,  Ber.,  1875,  8,  617. 

8  Dehn  and  Dewey,  Jovrn.  Amer.  Chem.  Soc.,  1911,  33,  1588. 


112  THE  NATURE  OF  ORGANIC  REACTIONS 

also  aldehydes  and  ketones,  cyanides  and  isocyanides,  cyanates  and 
isocyanates,  azo-  and  diazo-compounds,  &c.,  all  of  which  form 
additive  compounds,  are  readily  explained  on  the  theory  of  the 
unsaturation  of  certain  atoms. 

But  there  are  numerous  other  compounds  which  form  simple 
additive  compounds  where  the  explanation  is  not  so  simple.  In  the 
pyrones  *  the  oxygen  is  made  quadrivalent  in  order  to  afford  a  con- 
venient point  of  attachment  for  the  molecule  of  acid  with  which  they 
unite,  and  the  structure  of  the  quinhydrones  (Part  II,  p.  120)  is 
explained  in  the  same  way.  The  existence  of  molecular  compounds 
of  aromatic  hydrocarbons,  phenols,  and  amino-compounds  with  di-  and 
tri-nitrobenzene  and  picric  acid,  and  of  the  perbromides  of  bases,  &c., 
affords  further  examples  for  which  unsaturation  cannot  conveniently 
be  made  to  serve.  It  is  for  this  reason,  as  we  have  seen,  that 
Werner  has  introduced  the  notion  of  auxiliary  in  addition  to  ordinary 
or  principal  valencies  (see  p.  90). 

Nor  is  it  every  unsaturated  compound  that  is  capable  of  forming 
an  additive  compound ;  there  are,  for  example,  hydrocarbons  of  the 
ethylene  type  which  refuse  to  unite  with  hydrogen,  halogen  acid,  or 
halogen.  We  are  thus  confronted  with  conditions  in  which,  on  the 
one  hand,  atomic  unsaturation  is  for  some  reason  suspended,  and  in 
which,  on  the  other  hand,  addition  occurs  where  unsaturation  cannot 
be  assumed. 

A  study  of  the  conditions  determining  unsaturation  may  throw 
some  light  on  the  nature  of  this  property. 

Nef2  divides  unsaturated  compounds  into  three  categories,  namely , 
those  which  contain  a  single,  active,  unsaturated  carbon  atom,  such 
as  carbon  monoxide,  the  alkyl  and  acyl  isocyanides,  hydrocyanic 
acid,  fulminic  acid  and  its  salts,  and  mono-  and  di-halogen  substituted 
acetylenes.  They  exhibit  unsaturation  in  the  same  way  as  com- 
pounds of  the  second  or  ethenoid  type,  with  the  difference  that  the 
new  pair  of  atoms  or  groups  attach  themselves  to  the  same  carbon 
atom  instead  of  distributing  themselves  between  two.  The  bonds 
may  be  free  and  active,  or  latent  and  inert,  but  it  is  only  in  the 
former  condition,  according  to  Nef,  that  addition  can  occur.  The 
two  are  in  dynamic  equilibrium,  and  may  be  represented  in  the  case 
of  the  alkyl  isocyanides  in  the  following  manner : 

RN  =  C  =     ^±    RN  =  CZ| 

Active.  Inactive. 

The  process  of  addition  is  supposed  to  occur  by  partial  or  complete 

>  Trans.  Chem.  Soc.,  1809,  75,  710.  2  Joum.  Amer.  Chem.  Soc.,  1904,  26,  1549. 


REACTIONS  OF  UNSATURATED  COMPOUNDS       113 

dissociation  of  the  addendum  into  its  atoms  or  constituent  groups, 
which  then  unite  with  the  active  valencies  of  bivalent  carbon. 
Thus  the  isocyanides  form  additive  compounds  with  chlorine  in  the 
following  way : 

RN:C:  +  C1:C1    ->     RNiC/H      ->     RN: 

NGI 

The  other  additive  compounds  of  tho  isocyanides  have  already  been 
discussed  under  bivalent  carbon  (p.  65).  The  second  class  of 
unsaturated  compounds  includes  those  of  the  ethylene  type  which 
combine  by  direct  addition  to  a  pair  of  unsaturated  atoms,  and 
constitutes  the  largest  and  most  important  class. 

The  third  group  includes  those  closed  atomic  chains  such  as  cyclo- 
propane and  propylene  oxide,  which,  though  apparently  saturated, 
unite  with  halogens,  halogen  acids,  &c.,  like  the  olefines  (p.  180). 

Addition  (E  then  old  Compounds).  Ethenoid  compounds,  it  is 
well  known,  enter  as  a  rule  into  union  with  hydroxyl,  ozone,  the 
halogens,  halogen  acids,  sulphuric  and  hypochlorous  acid,  nitrosyl 
chlorides,  nitrogen  tri-  and  tetroxide,  and  less  frequently  with 
ammonia,  the  amines,  mercaptans,  and  alcohols.1  The  subject  has 
been  carefully  studied  by  Michael,*  who  has  laid  down  certain 
general  propositions,  which  he  regards  as  determining  the  course  of 
these  and  similar  reactions.  Adopting  the  principle  proposed  by 
Ostwald  that  '  every  system  tends  towards  that  state  whereby  the 
maximum  entropy  is  reached ',  Michael *  replaces  the  word  entropy 
by  chemical  neutralisation,  that  is,  the  neutralisation  of  the  chemical 
energies  or  affinities  of  the  reacting  atoms.  He  has  further  applied 
Ostwald's  idea  of  the  distribution  of  affinity  among  acids,  or  avidity,4 
to  the  formation  of  additive  compounds  under  the  term  distribution 
principle,  which  he  explains  as  follows : 

'If  two  unsaturated  atoms  A  and  B  are  present  in  an  organic 
molecule  which  exhibit  unequal  affinity  towards  C  and  D  of  the 
addendum  CD,  and  if  A  has  a  greater  affinity  for  C  than  B  has, 
addition  will  occur  if  the  affinity  of  AC  +  BD  is  greater  than  that  of 
CD,  and  the  more  readily  and  completely  the  larger  the  difference. 
In  this  process  of  addition  not  only  the  affinity  of  A  to  C  and  of 
B  to  D  comes  into  action,  but  also  that  of  A  to  D  and  of  B  to  (7,  and 
therefore  the  further  possibility  is  presented,  not  only  of  the  com- 
bination of  AC+BD,  but  of  AD  +  BC,  and  the  latter  in  increasing 

1  For  a  more  complete  list  see  J.  U.  Nef,  Annalen,  1897,  298,  206. 

a  /.  prakt.  Chem.,  1899,  60,  286,  410 ;  Ber.,  1906,  39,  2138. 

8  J.  prakt.  Chem.,  1899,  60,  292.  *  Thomsen,  Pogg.  Ann.,  1869,  135,  497. 

FT.  I  I 


114  THE  NATURE  OF  ORGANIC  REACTIONS 

proportion  the  nearer  the  two  combinations  AC+BD^AD  +  BO 
approach  one  another.  If  the  relations  are  changed  in  any  way  so 
that  the  affinity  of  A  to  C  exceeds  relatively  that  of  B  to  C,  the 
formation  of  AC+BD  must  increase  at  the  expense  of  AD  +  BO, 
and  if  B  has  a  greater  affinity  than  A  to  D  it  may  happen  that  the 
amount  of  AD  +  BC  becomes  so  small  as  practically  to  vanish.' 

This  principle,  taken  in  conjunction  with  that  of  maximum 
neutralisation,  will  determine  the  course  of  the  additive  process. 
The  latter  may  take  the  form  of  what  is  termed  by  Michael  the 
negative-positive  mle,  where  the  maximum  neutralisation  is  attained 
by  the  electronegative  atom  or  group  of  the  addendum  attaching 
itself  to  the  more  electropositive  atom  of  the  unsaturated  molecule, 
and  the  more  electropositive  atom  to  the  more  electronegative  part 
of  the  molecule.1  For  example,  in  propylene,  CH3 .  CH  :  CH2,  the 
electropositive  radical  CH3  will  influence  the  central  more  than  the 
end  ethenoid  carbon  by  rendering  it  more  electropositive.  Conse- 
quently, on  the  addition  of  hydrogen  iodide,  the  electronegative 
iodine  atom  will  be  mainly  attracted  to  the  central  carbon.  This 
proves  to  be  the  case.  At  the  same  time  a  small  amount  of  normal 
propyl  iodide  is  formed  in  agreement  with  the  principle  of 
distribution. 

If  in  place  of  hydrogen  iodide,  whose  constituents  lie  widely  apart 
in  the  electrochemical  series,  IC1  be  added  to  the  compound,  a 
certain  quantity  of  CH3  .  CHI .  CH2C1  should  be  formed  in  addition 
to  CH3.CHC1.CH2I.  If,  again,  BrCl  be  employed,  the  relative 
quantities  of  the  two  products  must  become  still  more  nearly  equal. 

Experiment  has  fully  confirmed  this  result,  for  Michael  found 
that  the  proportion  of  primary  to  secondary  chloride  in  the  first 
case  was  1 :  3,  and  in  the  second  5  :  7.2 

The  action  of  negative  groups  in  the  unsaturated  compound  will 
also  influence  the  result  by  rendering  the  neighbouring  ethenoid 
carbon  more  negative.  This  is  a  common  observation  among 
unsaturated  acids,  like  acrylic  acid,  with  a  strongly  negative 
carboxyl  group.  Here  the  halogen  of  the  halogen  acid  attaches 
itself  to  the  ft  carbon. 

From  the  above  considerations,  the  rule  laid  down  by  Markownikoff3 
that  the  halogen  of  a  halogen  acid  attaches  itself  to  the  least  hydro- 
genated  carbon,  though  by  no  means  free  from  exceptions,  will  be 
readily  understood ;  for  the  least  hydrogenated  carbon  will  usually 
be  the  one  situated  next  to  the  strongest  electropositive  hydrocarbon 

1  J.prakt.  Chem.,  1892,  46,  205.  2  J.prakt.  Chem.,  1892,  46,  345,  452. 

3  Annakn,  1870,  153,  256. 


ADDITION  (ETHENOID  COMPOUNDS)  115 

radical.  Let  us  take  the  case  of  a  substituted  olefine  such  as 
/S-bromopropylene,  CH3  .  CBr  :  CH2.  The  addition  of  hydrogen 
bromide  produces  /2/2-dibromopropane.1  The  effect  here  is  due, 
according  to  Michael,  to  the  neutral  character  of  the  carbon  atom, 
whereby  the  mutual  attraction  of  the  bromine  atoms  in  the  free 
state  is  still  exerted,  under  the  concurrent  influence  of  the  electro- 
positive methyl  group.  If,  on  the  other  hand,  the  bromine  occupies 
the  a  position,  CH3 .  CH :  CHBr,  the  attraction  of  the  bromine  atom 
as  well  as  the  proximity  of  the  methyl  group  act  in  opposition  ;  the 
hydrogen  bromide  distributes  itself,  so  that  both  propylene  bromides 
are  formed,  namely,  CH3.  CHBr.  CH2Br,  CH3 .  CH2 .  CHBr2. 

Michael 2  considers  that  in  longer  chains  reactivity  may  be 
influenced  and  modified  by  spatial  considerations,  and  that,  for 
example,  a  carbon  group  in  position  5  and  6  relatively  to  the 
unsaturated  carbon  atom  may,  by  its  tendency  towards  ring-forma- 
tion, and,  therefore,  by  its  proximity  to  the  unsaturated  carbon 
atoms,  determine  the  character  of  the  product.  In  this  way  either 
the  direct  or  indirect  influence  of  each  atom  will  be  exerted  according 
to  its  position,  and  determine  the  course  of  the  reaction,3  that  of 
the  atoms  in  direct  connection  with  the  reacting  group  naturally 
predominating. 

Much  the  same  conditions  as  those  which  determine  addition 
should  affect  the  removal  of  halogen  acids  by  alkalis,  and  some  of 
the  experimental  results  will  now  be  briefly  referred  to. 

In  propylene  bromide,  for  example,  the  effect  of  the  positive 
methyl  group  will  not  only  be  distributed  between  the  two  other 
carbon  atoms,  but  will  be  directed  in  a  greater  degree  towards  the 
retention  of  the  bromine  atom  in  the  ft  position.  It  has  been  found 
that  the  proportion  of  CH3  .  CBr  :  CH2  to  CH3 .  CH :  CHBr  is  two 
to  one.  As  /?-bromopropionic  acid  is  more  readily  formed  from 
acrylic  acid  than  the  a  compound,  the  former  loses  hydrogen  bromide 
more  readily.  Isobutylene  yields  tertiary  butyl  bromide,  and  it  is 
found  that  the  latter,  of  all  the  isomers,  is  most  readily  converted 
into  isobutylene. 

Similarly  with  the  dihalogen  compounds;  the  more  readily 
bromine  is  added,  the  more  easily  is  it,  as  a  rule,  removed. 
Generally  speaking,  the  hydrogen  of  the  least  hydrogenated  carbon 
is  detached  ; 4  but  its  removal  depends  upon  the  proximity  of  methyl 
groups,  which  by  increasing  the  positivity  of  the  carbon  diminishes 

1  Reboul,  Ann.  Chim.  Phys.,  1878,  14,  465. 

2  J.  prakt.  Chem.,  1892,  46,  335. 

1  See  van  't  Hoff's  Ansichtm,  vol.  i,  p.  284,  vol.  ii,  p.  252 
*  Saytzeff,  Annalen,  1875,  179,  280. 

I  2 


116  THE  NATURE  OF  ORGANIC  REACTIONS 

its  affinity  for  hydrogen.  (CH3)2CH .  CHBr .  CH3  gives  mainly 
trimethylethylene  (CH3)2 .  C :  CH .  CH3,  and  a  little  isopropyl- 
ethylene  (CH3)2CH .  CH :  CH2. 

The  little  that  has  been  systematically  investigated  on  the  addition 
of  hypochlorous  acid,  ammonia,  and  alcohol  is  referred  to  by 
Michael.1 

In  the  above  examples  we  have  considered  mainly  the  nature  of 
the  addenda.  We  will  now  extend  the  inquiry  into  the  eifect  on 
addition  of  introducing  other  groups  into  the  ethenoid  molecule  in 
place  of  hydrogen.  A  considerable  amount  of  work  has  been  done 
on  this  subject  by  Klages,  Bauer,  and  Nef. 

Addition  of  Hydrogen.  Klages  2  has  studied  the  reduction  of 
two  series  of  ethylene  derivatives,  in  one  of  which  a  hydrogen  atom 
is  replaced  by  phenyl,  and  in  the  other  by  carboxyl.  Other  hydrogen 
atoms  are  replaced  by  methyl,  benzyl,  and  phenyl  groups.  The 
reduction  appears  to  be  inhibited  where  two  methyl  groups  replace 
both  the  hydrogen  atoms  attached  to  the  same  carbon  atom ;  in 
other  words,  by  augmenting  the  positive  character  of  the  carbon 
group  affinity  for  hydrogen  is  diminished.  Thus,  dimethyl  and 
ethyldimethyl  styrene  C6H5CH  :C(CH3)2,  C6H5C(C2H5) :  C(CH3)2 , 
/J-dimethylacrylic  acid  COOH .  CH  :  C(CH3)2,  and  teraconic  acid 
COOH.C(CH2COOH):C(CH3)2,  are  either  reduced  with  great 
difficulty  or  not  at  all.  The  same  applies  to  terpinolene  (Part  III, 
p.  257)  and  to  methylheptenone  (Part  III,  p.  257),  both  of  which 
contain  the  group  C  :  C(CH3)2. 

Addition  of  Bromine.  Bauer3  has  examined  the  effect  of 
substituents  on  the  additive  power  of  ethenoid  compounds  for 
bromine.  His  results  are  formulated  in  the  following  statement  : 
*  the  tendency  of  a  carbon  double  bond  to  add  bromine  is  diminished 
if  in  the  case  of  both  carbon  atoms  reduplication  of  carboxyl,  ester, 
phenyl  groups,  or  bromine  has  taken  place.'  Here  the  accumu- 
lation of  negative  groups  affects  the  addition  of  negative  atoms. 
In  the  acrylic  acid  series,  the  substitution  of  hydrogen  by  one  or 
more  methyl  groups  or  one  bromine  atom  attached  to  either  carbon 
does  not  prevent  addition  ;  but  neither  tribromacrylic  nor  dibromo- 
crotonic  acid  combine.  Further,  dimethylfumaric  acid  (pyro- 
cinchonic  acid),  diethylfumaric  acid  (xeronic  acid),  dibromo-  and 
methylbromo-fumaric  acid,  acetylene  tetracarboxylic  and  a-phenyl- 
cinnamic  acid  do  not  lend  themselves  to  addition  of  bromine, 

1  J.  praM.  Chevn..  1899,  60,  431,  463,  467.  2  Bcr.,  1904,  37,  924,  1721,  2301. 

8  Bar.,  1904,  37,  3317. 


ADDITION  OF  BROMINE  117 

whereas  both  maleic  and  fumaric,  methylfumaric  and  bromomaleic 
acids  combine.  Here  the  multiplication  of  both  positive  and  negative 
groups  prevents  addition,  a  fact  which  steric  hindrance  may  possibly 
serve  to  explain. 

Sudborough  and  Thomas1  have  shown  that  the  unsaturation  of 
/?y  unsaturated  acids  is  much  greater  than  that  of  a/3  acids,  and  the 
rapid  addition  of  bromine  in  the  former  case  serves  as  a  method  for 
distinguishing  the  two  classes.  The  difference  in  the  case  of 
the  a/3  acids  is  attributed  to  conjugation,  which  is  explained  on 
p.  133. 

The  addition  of  halogens  is  also  modified  by  light,  and  will  be 
referred  to  in  the  section  on  photochemistry  (Part  II,  p.  141). 

It  is  an  interesting  fact,  that  whereas  cinnamic  acid  and  crotonic 
acid  do  not  unite  with  iodine,  phenylpropiolic  acid  and  tetrolic 
acid,  CH3C  i  C .  COOH,  combine  with  two  atoms  of  the  element. 

Turning  to  the  hydrocarbons,  stilbene  C6H5CH  :  CH .  CCH5  and 
its  monomethyl  and  monobromo  derivative  add  bromine,  but  not  the 
dibromo  derivative.  Where  both  phenyl  groups  are  attached  to  the 
same  carbon  atoms  as  in  diphenylethylene  (C6H5)2C :  CH2  and  its 
mono-  and  di-methyl  derivatives,  bromine  addition  takes  place, 
but  is  prevented  in  (CGH5)2C  :  C(C6H5)2,  (C6H5)2C :  CHBr,  and 
(C6H5)2C:CBrCHo,  that  is,  where  two  phenyl  groups  or  bromine 
are  attached  to  the  second  ethenoid  carbon.  The  presence  of  chlorine 
and  cyanogen  produce  the  same  effect  as  bromine.2  A  further  fact 
of  interest  mentioned  by  Bauer  is  that  phenylcinnamic  nitrile  adds 
bromine,  forming  a  definite  bromide,  but  a  nitro  group  in  the  para 
position  prevents  the  addition.  The  w-nitro  compound,  on  the 
other  hand,  yields  a  definite  additive  compound,  whilst  the  o-nitro 
compound  occupies  a  middle  position,  bromine  being  partially 
decolorised  without  evolution  of  hydrogen  bromide. 

°') 

m-  [NOAH4v  yC6H5 

H  /C:C\ 

H/         XJN 

Nitrophenylcinnamic  nitrile. 

The  retarding  effect  of  phenyl,  carboxyl,  and  cyanogen  follow  in 
increasing  order,  C6H5  <  COOH  <  CN,  which  agrees  with  the  affinity 
constants  of  the  acids  in  which  they  occur  : 

K 

Phenylacetic  acid     C6H5  .  CH2  .  COOH        0  00556 
Malonic  acid  COOH .  CH2 .  COOH       0-045 

Cyanacetic  acid         CN .  CH2 .  COOH  0-37 

1  Trans.  Chem.  Soc.,  1910,  97,  715.  a  Bauer,  J.'prakt.  Chem.,  1905,  72,  201. 


118  THE  NATURE  OF  ORGANIC  REACTIONS 

The  results  of  these  observations  appear  to  fall  in  with  Michael's 
neutralisation  or  positive  -negative  rule  ;  for  the  addition  of  positive 
hydrogen  atoms  is  retarded  by  reduplication  of  positive  radicals  in 
the  ethenoid  molecule,  and  negative  bromine  atoms  by  the  presence 
of  negative  radicals.  On  the  other  hand,  Biltz  *  has  pointed  out  that, 
although  tetraphenylethylene  does  not  unite  with  bromine,  the 
closely  allied  compounds  tetraphenylene-ethylene  and  its  oxide 
combine,  though  in  the  second  case  with  difficulty. 


I  C:C<       |  0  >C:C  0 

CGH/      \c6H4  XH/      XCGH/ 

Tetraphenylene-ethylene.  Tetraphenylene-ethylene  oxide. 

Also,  diphenyldichlorethylene,  phenylmono-,  di-,  and  tri-chlor- 
ethylene,  as  \vell  as  tetrachlorethylene  in  sunlight,  form  additive 
compounds  in  spite  of  the  multiplication  of  negative  groups. 

(C6H6)2C:CC12      CGH5CH:CHC1      C6H5CH:CC12      C6H5CC1:CC12 

Diphenyldiehlor-  Phenylchlor-  Phenyldichlor-          Phenyltrichlor- 

ethylene.  ethylene.  ethylene.  ethylene. 

But  addition  is  inhibited  in  the  case  of  diphenyldinitroethyleno, 
CCH5C(N02):C(N02)C6H5. 

The  evidence  is  veiy  conflicting.  Bauer2  adopts  Hinrichsen's 
view  that  negative  groups  in  sufficient  number  and  strength  weaken 
the  fourth  valency  of  carbon,  just  as  phosphorous  pentachloride 
overloaded  with  negative  atoms  loses  chlorine  on  heating,  and  passes 
to  a  state  of  lower  and  more  stable  valency.  The  valency  of  carbon, 
in  the  same  way,  when  overloaded  with  negative  atoms  or  groups, 
tends  to  shrink  and  become  tervalent.  From  this  point  of  view  there 
is  nothing  remarkable  in  the  existence  of  triphenylmethyl  (p.  60). 

Exactly  similar  views  have  been  expressed  by  Michael3  on  the 
instability  of  carbon  compounds  when  charged  with  either  negative 
or  positive  atoms  or  groups.  Methane  is  a  stable  neutral  compound 
because  the  negative  carbon  is  neutralised  by  the  four  positive 
hydrogen  atoms  ;  but  if  hydrogen  is  replaced  by  an  electropositive 
metal,  as  in  the  organo-metallic  compounds,  there  is  a  surplus  of 
positive  polarity,  and  a  consequent  loss  of  stability.  The  combined 
loss  of  stability  and  active  valency  is,  no  doubt,  a  gradual  one,  and 
varies  in  different  compounds,  so  that  the  addition  or  removal  of 
bromine  is  probably  a  reversible  process,  the  balance  of  which  may 
shift  from  one  side,  where  no  addition  occurs  under  any  circum- 

1  Annalen,  1897,  296,  231,  263.  2  Annalen,  1904,  336,  223. 

3  J.  praht.  Chem.,  1899,  60,  802. 


ADDITION  OF  NITROSYL  CHLORIDE  119 

stances,  to  the  other,  where  the  ethylene  compound  is  wholly 
converted  into  a  definite  and  stable  bromide. 

Addition  of  Nitrosyl  Chloride.  The  union  of  nitrosyl  chloride 
with  unsaturated  compounds  was  first  studied  by  Tilden,1  who 
found  that  addition  occurs  in  the  case  of  limonene,  pinene,  tri- 
methyl-,  tetramethyl-,  and  methylpropyl-ethylene,  normal  octylene, 
phenylethylene  (cinnamene),  and  diphenylethylene,  oleic  and 
elaidic  acids,  anethole  and  isosafrole  ;  but  not  with  acenaphthylene, 
eugenol,  safrole,  w-nitrocinnamene,  crotonic,  isocro tonic,  fumaric, 
and  maleic  acids.  There  appears  to  be  no  relation  between  the 
additive  power  for  nitrosyl  chloride  and  that  for  bromine. 

Addition   of  Nitrogen   Trioxide.        The   property   of  forming 
additive  compounds  with  N203  is  also  found  among  the  terpenes. 
The  nature  of  the  product  may  vary  according  to  the  environment, 
giving  rise  to  nitroso-nitro  compounds  or  nitro-oximes.' 
_C C—  — C C— 

!       I  I      II 

N02  NO  NO2  NOH 

Nitroso-nitro.  Nitro-oxime. 

Addition  of  Nitrogen  Tetroxide.  Many  of  the  terpenes  and 
unsaturated  ketones 3  are  known  to  form  additive  compounds  with 
nitrogen  tetroxide,  forming  nitrosates  containing  the  group, 

— C C— 

I         I 
N02  ONO 

which,  in  the  case  of  unsaturated  ketones,  readily  loses  HN02,  and 
passes  into  unsaturated  nitro  compounds.  Schmidt 4  has  shown 
that  with  diphenylacetylene  both  cis  and  trans  stereoisomers  of 
dimtrodiphenylethylene  are  formed, 

CGH5.C  =  C.C6H5 

I        [ 
N02  NO2 

and  Biltz 5  has  found  that  this  property  is  shared  by  tetrachlor-  and 
tetrabrom-ethylene.  In  the  case  of  the  tetraiodo  compound,  sub- 
stitution of  the  iodine  occurs. 

Addition  of  Hydroxyl  and  Ozone.  A  characteristic  property  of 
the  ethenoid  carbon  atom  is  its  power  of  taking  up  two  hydroxyl 

1  Trans.  Chem.  Soc.,  1894,  1,  324. 

2  Wieland,  Annalen,  1903,  328,  154  ;  1903,  329,  225  ;  1905,  340,  63. 

3  Wieland  and  Bloch,  Annalen,  1905,  340,  163. 

4  £tr.,  1901,  34,  619.  5  Ber.,  1902,  35,  1528. 


120  THE  NATUKE  OF  ORGANIC  REACTIONS 

groups  when  oxidised  by  a  dilute  and  neutral  solution  of  perman- 
ganate, usually  at  the  ordinary  temperature.  This  reaction  has 
been  utilized  in  ascertaining  the  position  of  a  double  link  as  well  as 
in  effecting  the  cleavage  of  the  molecule  by  further  oxidation  at 
this  point  :  >  C  =  C  <  +  H20  +  0=>  C(OH)  -  C(OH)  <.  Many  examples 
of  this  reaction  will  be  discussed  in  later  chapters.  Another  property 
which  appears  to  be  shared  by  acetylene  compounds  is  the  union  of 
ethenoid  compounds  with  one  molecule  of  ozone,  forming  a  class  of 
compounds  known  as  ozonides. 

>C:C<+03=>C  -  C<    or    >C  —  C< 

II  II 

0—  O—  O  O  —  0 

v 

O 

The  formation  and  properties  of  these  compounds  have  been 
exhaustively  studied  by  Harries  and  his  co-workers.1  They  are 
obtained  by  passing  ozonised  oxygen  (containing  about  five  per  cent. 
of  ozone)  into  a  solution  of  the  unsaturated  compound  in  an  inert 
solvent  along  with  a  current  of  carbon  dioxide,  which  diminishes 
the  risk  of  explosion,  some  ozonides  being  extremely  explosive.  They 
are  thick  colourless  oils,  syrups,  or  gelatinous  masses,  which  liberate 
iodine  from  potassium  iodide  and  bleach  permanganate  and  indigo. 
They  have  a  peculiarly  unpleasant  and  suffocating  smell,  and  some, 
such  as  the  ozonides  of  mesityl  oxide  and  acrolein,  are  explosive, 
but  not  those  of  the  unsaturated  hydrocarbons,  the  simpler  members 
of  which  are  sufficiently  stable  to  be  distilled  in  vacuo.  With  water 
they  decompose  at  the  original  double  bond  into  aldehyde  or  ketone 
and  hydrogen  peroxide. 


0  +  H90  =  2HCHO  +  H0 
CH 

Ethylene  ozonide.  Formaldehyde. 

In  other  cases,  where  excess  of  ozone  is  used,  the  ozonide  breaks  up 
and  gives  the  peroxide  of  the  one  carbon  group  and  the  aldehyde 
or  ketone  of  the  other. 


C  --  O,  CH3X        O 

I  >0  =  >C<     4-  RCHO 

RCH—  (K  R/    \6 

The   formation   of  ozonides   may   be   used  for  determining  the 
presence  and,  frequently,  the  position  of  a  double  bond,  and  the 

1  Annahn,  1905,  343,  311  ;  1915,  410,  1. 


ADDITION  OF  HYDROXYL  AND  OZONE  121 

process  has  been  applied  in  the  case  of  pulegone,  pinene,  and  other 
compounds. 

The  fact  that  benzene  forms  a  triozonide  may  therefore  be  taken 
as  evidence  of  the  Kekule  formula.  This  compound  breaks  up  with 
water  like  other  ozonides,  giving  three  molecules  of  glyoxal. 


, 
H 


CHO 

/-  CHO 

0<  +  3H00     -*     | 

X0—  HCv'cH,  CHO 

CH  CHO 


—  O 

Naphthalene,  however,  only  unites  with  two  molecules  of  ozone, 
both  of  which  are  attached  to  the  same  nucleus,  and  consequently, 
according  to  Harries,  the  two  nuclei  are  differently  constituted. 

The  action  of  ozone  on  aldehyde  and  ketone  groups  is  to  furnish 
one  additional  atom  of  oxygen,  and  form  a  peroxide,  so  that  a 
substance  like  mesityl  oxide,  which  contains  a  ketoue  group  in 
addition  to  an  ethylene  linkage,  unites  with  four  atoms  of  oxygen,  the 
product  breaking  up  with  water  into  acetone  (or  acetone  peroxide), 
pyruvic  aldehyde,  and  hydrogen  peroxide  : 

(CH3),C  :  CH  .  CO  .  CH3  +  03  +  O  =  (CH  )2C—  CH  .  C  .  CH3 

I       I        li 
O     O      O 


O          O 
(CH  )2C-CH .  C .  CH3  +  2H20  =  (CH3)2CO  +  CHO .  CO .  CH3  +  2H203 

O    O       O 

V    ii 

O          O  /O 

or,         +  H2O  =  (CH-JC/  |  +  CHO .  CO .  CH3  +  H2O2 

Autoxidation.  The  behaviour  of  unsaturated  compounds  towards 
ozone  leads  directly  to  the  action  upon  them  of  free  oxygen,  and  to 
the  explanation  of  the  phenomenon  known  as  autoxidation,  which 
was  first  studied  by  Schonbein.  The  property  which  turpentine  oil 
possesses  when  exposed  to  air  of  absorbing  oxygen,  which  is  thereby 
rendered  active  and  capable  of  bleaching  indigo,  separating  iodine 
from  potassium  iodide,  oxidising  arsenious  to  arsenic  acid,  &c.,  has 
long  been  known,  and  the  induced  activity  has  been  variously 
ascribed  to  the  formation  of  ozone,  hydrogen  peroxide,  and  atomic 


122  THE  NATUKE  OF  ORGANIC  REACTIONS 

oxygen.  A  different  interpretation  of  the  process  has  been  offered 
by  Moritz  Traube  and  Engler  and  Weissberg1  on  the  following 
grounds  :  turpentine  oil  will  retain  its  oxidising  properties  for  years  in 
the  dark  in  absence  of  air,  a  condition  which  would  scarcely  obtain  if 
ozone  or  atomic  oxygen  were  in  contact  with  so  oxidisable  a  substance 
as  turpentine.  The  oxygen  which  turpentine  absorbs  is  not  dis- 
placed by  passing  inert  gases  through  the  liquid,  indicating  some 
form  of  combination.  The  activity  cannot  be  due  to  dissolved 
hydrogen  peroxide,  since  the  latter  cannot  be  removed  by  shaking 
with  water,  whereas  from  an  artificially  prepared  mixture  it  is 
completely  extracted.  Moreover,  oxidised  turpentine  oil,  unlike 
hydrogen  peroxide,  separates  iodine  from  potassium  iodide  in  absence 
of  an  acid,  and  gives  no  blue  colour  with  chromic  acid  solution  and 
ether  such  as  a  trace  of  hydrogen  peroxide  will  produce.  On  the  other 
hand,  the  oxidised  turpentine  gives  the  yellow  colour  with  titanic 
acid,  characteristic  of  all  peroxides.  The  conclusion  arrived  at  by 
the  authors  is  that  the  oxygen  attaches  itself  in  the  molecular  form 
to  the  substance,  yielding  a  peroxide  which  may  undergo  intra- 
molecular rearrangement  into  the  ordinary  atomic  form,  or  may 
give  up  a  portion  of  its  oxygen  to  an  oxidisable  substance  in  its 
vicinity.  In  this  way  many  substances  which  are  not  directly 
oxidisable  by  free  oxygen  can  be  oxidised  indirectly  by  the  peroxide. 
The  authors  of  the  theory  term  the  peroxide  or  moloxide  the 
autoxidator,  the  substance  indirectly  oxidised  the  acceptor,  and 
formulate  the  process  as  follows  : 

A02      +      B     -»      AO  +  BO 

Autoxidator.     Acceptor. 

A  behaviour  precisely  similar  to  that  of  turpentine  has  been 
observed  in  the  case  of  other  unsaturated  hydrocarbons,  amylene,  tri- 
methylethylene,  hexylene,  fulvene  and  its  derivatives  (Part  II,  p.  92), 
&c.,  and  may  be  represented  as  follows : 

— C=-C—  +  0      =    -C— C— 


0-0 


in  which  molecular  oxygen  adds  itself  to  the  ethenoid  carbon  atoms 
after  the  manner  of  ozone. 

The  discovery  by  Baeyer  and  Villiger2  of  the  existence  of  a 
definite  though  highly  unstable  peroxide  of  benzaldehyde  has 
afforded  strong  evidence  in  favour  of  the  above  view.  The  substance 

1  Vorgange  der  Autoxydation.     Vieweg,  Brunswick,  1904. 

2  £er.,  1900,  33,  858,  1569. 


AUTOXIDATION  123 

was  obtained  by  the  action  of  hydrogen  peroxide  on  benzaldehyde 
as  a  colourless  crystalline  compound  having  an  acid  character  and 
forming  salts.  According  to  Engler  and  Weissberg  it  is  produced 
by  addition  of  molecular  oxygen  followed  by  intramolecular  change. 

O 
C6IL-CH :  O    ->    CGH  CH<^>0    ->    C6H5C .  0 .  OH 

V  !' 

o 

Benzoyl  hydroperoxide. 

Benzoyl  hydroperoxide  has  similar  properties  to  oxidised  turpentine, 
inasmuch  as  it  is  not  only  capable  of  oxidising  a  second  substance 
such  as  indigo,  but  can  react  upon  itself  and,  by  parting  with  an 
atom  of  oxygen  to  a  second  molecule  of  benzaldehyde,  yield  two 
molecules  of  benzoic  acid : 

C6H3CHO+C6H5C03H  =  2C6H5COOH 

A  similar  process  has  been  observed  in  the  case  of  triethylphosphine, 
which,  by  absorption  of  oxygen,  forms  a  peroxide,  (C2H5)3PO2, 
capable  of  reacting  on  the  unchanged  substance,  giving  two 
molecules  of  monoxide : 

(C2H5)3P02+(C2H5)3P  =  2(C2H5)3PO 

Many  other  examples  of  peroxide  formation  by  absorption  of  free 
oxygen  might  be  quoted,  such  as  the  conversion  of  phenylhydroxyl- 
amine  into  azoxy benzene,1  and  /?-methylhydrindone  into  benzyl- 
methylketone  o-carboxylic  acid,2  but  sufficient  has  been  stated  to 
illustrate  the  parallelism  which  exists  in  the  behaviour  of  free 
oxygen  and  ozone. 

But  in  addition  to  the  secondary  processes  above  described, 
namely,  the  interaction  of  the  peroxide  compound  with  a  foreign 
oxidisable  substance,  and  also  with  itself,  other  secondary  changes 
may  and  often  do  occur,  such  as  the  polymerisation  of  the  peroxide, 
observed  in  the  case  of  acetone  peroxide,  and  the  action  of  water  on 
the  peroxide,  which  may  lead  to  the  formation  of  hydrogen  peroxide. 
The  appearance  of  hydrogen  peroxide  wrhen  oxidised  turpentine  is 
left  in  contact  with  water  has  been  explained  in  this  way : 

0    Hv  /O.OH 

|  +      >0    -»    A<  ->    A0  +  H202 

H/  M)H 

More  recently,  peroxides  have  been  used  for  oxidising  the  ethenoid 


1  Kipping  and  Sal  way,  Trans.  Cheni.  Soc.,  1909,  05,  156. 
5  Bamberger,  Ber.,  1894,  27,  1551. 


124  THE  NATURE  OF  ORGANIC  REACTIONS 

group  by  delivering  up  an  atom  of  oxygen.     Ethylene  oxides  can  be 
prepared  in  this  way  by  the  use  of  benzoyl  hydroperoxide. 

O 

>C  =  C<+C6H5C03H=>(J— <J<  + C6H5C02H 

The  application  of  other  organic  peracids  to  the  oxidation  of  anhy- 
drides has  also  been  studied.1 

Heterogeneous  Addition.  We  have  so  far  considered  the  nature 
of  addition  where  the  constituents  of  the  addendum  are  similar,  as 
in  bromine,  or  dissimilar,  as  in  hydrogen  iodide,  and  again  where 
the  ethenoid  carbon  atoms  are  linked  to  different  groups.  There 
is  a  third  case  where  both  the  ethenoid  carbons  are  attached  to 
different  radicals,  and  the  addendum  consists  of  heterogeneous  con- 
stituents. Examples  of  this  type  are  considered  on  p.  203,  and  need 
not  be  referred  to  at  length.  The  most  interesting  cases  are  perhaps 
those  reactions  in  which  the  alkyl  and  acyl  halide  react  with  the 
metallic  compounds  of  acetoacetic  ester  and  Michael's  reaction 
(p.  202).  Here  the  electrochemical  characters  again  appear  to 
determine  the  course  of  the  additive  process,  the  positive  and 
negative  groups  on  both  sides  distributing  themselves  in  such  a 
way  as  to  produce,  according  to  Michael,  the  maximum  neutralisation 
of  affinities. 

For  example,  the  negative  iodine  atom  of  the  alkyl  iodide  attaches 
itself  to  the  carbon  which  is  rendered  positive  by  methyl  and  the  ONa 
group,  and  the  positive  alkyl  group  to  the  negative  carbon  made 
negative  by  the  associated  carboxyl  group,  that  is  to  say,  the 

ONa 

+  I 

CH3 .  C(ONa) :  CH .  COOC2H3      CH;3 .  0— CH .  COOC2H5 

I  CH3  I     CH3 

=  CH3 .  CO .  CH(CH3) .  COOC2H5  +  Nal 

substitution  is  preceded  by  addition,  an  assumption  which  is  by  no 
means  improbable. 

In  Michael's  reaction  similar  conditions  are  supposed  to  prevail. 
The  union  of  cinnamic  ester  and  sodium  malonic  ester  probably 
takes  place  as  follows  : 

+       - 
C6H5 .  CH  :  CH .  COOC2H5  CCH- .  CH .  CHNa .  COOC2H5 

+  I 

(C2H,OOC)2CH    Na  =  (C2H5OOC)2CH 

.  Citem.  Journ.,  1905,  32,  143. 


HETEROGENEOUS  ADDITION  125 

An  interesting  question  arises  as  to  what  would  occur  if  in  the 
first  of  these  two  reactions  the  metal  were  made  less  positive  and 
the  addendum  more  negative.  What,  in  short,  would  happen  if 
silver  were  substituted  for  sodium,  and  an  acyl  for  an  alkyl  radical  ? 
The  subject  has  been  investigated  by  Michael.1  He  finds  that  if 
the  relations  of  the  two  unsaturated  atoms  are  so  changed  that  their 
affinity  to  methyl  is  diminished  more  than  that  of  the  metal-oxygen, 
the  tendency  of  the  reaction  will  be  towards  substitution  rather  than 
addition.  Silver  acetoacetic  ester  and  methyl  iodide  still  give'  methyl- 
acetoacetic  ester,  but  less  readily  and  with  decreased  yield.  If  the 
negative  chloroformic  ester  is  substituted  for  methyl  iodide,  sub- 
stitution occurs  and  not  addition,  and  the  acidic  group  attaches 
itself  to  oxygen.2 

If,  again,  the  ketone  group  is  made  more  acidic,  as,  for  example, 
in  oxaloacetic  ester,  C2H5OOC.  CO.  CH2.  COOC2H5,  the  alkali 
compound  furnishes  only  a  poor  yield  of  C-alkyl  derivative,  but  an 
excellent  yield  of  the  0-alkyl  compound,  especially  if  the  less  positive 
silver  salt  is  used.  - 

The  action  on  sodium  acetoacetic  ester  of  a  strongly  negative 
halide  compound,  such  as  acetyl  chloride,  is  interesting,  for  its 
tendency  to  unite  with  oxygen  is  small  in  spite  of  the  presence  of 
the  strongly  electropositive  alkali  metal,  and  consequently  diaceto- 
acetic  ester  is  formed : 

CH3COC1  +  CH3 ,  C(ONa) :  CH  .  COOC2H5 
=  (CH3 .  CO)2CE .  COOC2H5  +  NaCl 

It  is  not,  however,  clear  from  Michael's  theory  why  the  union 
between  acetyl  chloride  and  acetoacetic  ester,  in  presence  of  so  weak 
a  base  as  pyridine,  should  give  rise  to  acetoxycrotonic  ester, 
CH3 .  CO(CO  .  CH3) :  CH  .  COOC2H5  rather  than  its  isomer. 

Nef s  has  expressed  much  the  same  view,  namely,  that  the  metal 
is  attached  to  oxygen,  and  that  alkyl  and  acyl  halides  may  react  by 
addition.  He  has  shown  that  by  the  action  of  acetyl  chloride  on 
the  sodium  compound  both  products,  namely,  a  little  0-acetyl  along 

1  J.prakt.  Chem.,  1899,  60,  316  ;  see  also  Lander,  Trans.  Chem.  Soc.,  1900,  77, 

2  This  is  in  accordance  with  a  more  general  law  enunciated  by  Michael, 
whereby  carbon,  when  attached  to  negative  atoms  or  groups,  shows  less  tendency 
to  combine  with  itself  (polymerise).     Carbon  monoxide  can  exist  as  a  single 
molecule,  but  in  union  with  metals  polymerises,  giving  (COK)6(CO)6Ni,  (CO)6Fe. 
On  the  other  hand,  the  non-existence  of  methylene  and  methyl  is  due  to  the 
opposite  tendency  of  the  presence  of  electropositive  atoms  to  cause  polymerisa- 
tion (J.prakt.  Chem.,  1899,  60,  295). 

5  Annalen.  1891,  266,  52  ;  1893,  276,  235  ;  1894,  280,  314. 


12G  THE  NATURE  OF  ORGANIC  REACTIONS 

with  the  C-acetyl  derivative  are  formed.  The  main  difference  be- 
tween these  observers  is  that  Nef  regards  both  the  free  acetoacetic  ester 
as  well  as  its  sodium  derivative  as  possessing  the  hydroxyl  formula, 
a  view  which  has  since  been  disproved.  Moreover,  he  assumed  that 
the  halogen  united  with  the  a-hydrogen  of  the  ester  rather  than 
with  the  sodium  atom.  He  bases  the  latter  view  on  the  observation 
that  benzyl  chloride,  and  also  acetyl  and  benzoyl  chloride  acting 
on  the  sodium  compound,  give  both  mono  and  dialkyl  and  acyl 
derivatives,  which  he  expresses  as  follows  : 

CH3.CONa:CH.COOC2H5  =  CH3.C(ONa):C(C7H7).COOC2H,  +  HCl 

6l         C7H7 
CH3.CONa:C(C7H7).COOC2H5  =  CH3.CO.C(C7H7)2.COOC2H-  +  NaCl 

Cl        C7H7 

It  seems  improbable  that  if  sodium  chloride  were  eliminated  at  the 
first  stage  the  product,  which  contains  a  benzyl  group  and  is  there- 
fore more  positive,  should  decompose  the  sodium  chloride  and  yield 
a  sodium  compound  capable  of  reacting  with  a  second  molecule  of 
benzyl  chloride.  He  concludes  that  the  direct  exchange  of  metal 
is  not  possible.1 

There  are,  however,  other  explanations  of  the  above  processes  not 
involving  addition.  The  change  of  O-compound  to  C-compound 
might  occur  after  substitution  under  certain  conditions,  although 
ethoxycrotonic  and  ethoxyfumaric  ester  are  comparatively  stable 

C2H5O.C.CH3  C2H5O.CH 

HC .  COOC2H5  OH .  COOC2H5 

Ethoxycrotonic  ester.  Ethoxyfumaric  ester. 

substances,  and  it  is  not  probable  that  in  these  two  cases  such  a 
shifting  of  the  alkyl  group  is  likely  to  occur.  The  acyl  derivatives  of 
acetoacetic  ester,  on  the  other  hand,  are  known  to  undergo  isomeric 
change  of  this  character  (Part  II,  p.  363). 

Dismissing  the  theory  of  isomeric  change  after  replacement  as 
improbable,  there  is  another  view  which  has  been  advanced  by 
W.  Wislicenus.2  Direct  substitution  of  metal  by  radical  occurs 
under  constraint,  and  is  usually  effected  by  means  of  an  insoluble 
compound  (silver  salt)  in  a  non-dissociating  medium  (ether,  benzene, 
&c.).  Replacement  by  a  metal  (alkali)  in  a  dissociating  solvent  and 
at  a  higher  temperature  brings  about  a  '  free  reaction ',  and  with  it 

1  Annakn,  1891,  266,  11G- 

2  '  Tautowerie ',  Ahrens'  Vortr&ge,  1898,  2,  249. 


ADDITION  PEODUCTS  OF  KETONES  127 

indirect  substitution.  This  latter  effect  is  supposed  to  depend  upon 
the  reversible  nature  of  the  free  bond  of  the  organic  residue  on 
removal  of  the  metal,  which  may  be  expressed  in  the  case  of 
acetoacetic  ester  as  follows  : 

CH3.CO:CH.COOC2H5    ±^    CH3 .  CO .  CH .  COOC2H5 

and  it  will  thus  enable  the  C-derivative  to  be  formed.  The  first,  or 
constrained  process,  produces  an  0-derivative  ;  the  second,  or  free 
reaction,  a  C-derivative. 

But  if  the  formation  of  an  0-derivative  in  acetoacetic  ester  depends 
on  a  constrained  reaction,  it  is  difficult  to  account  for  the  fact,  dis- 
covered by  Lander,1  that  90  per  cent,  of  C-ether  is  formed  by  the 
action  of  ethyl  iodide  in  presence  of  silver  oxide  (which  gives  much 
the  same  result  as  the  silver  compound). 

Perhaps  the  most  satisfactory  explanation,  as  suiting  the  most 
varied  conditions  has  been  supplied  by  Lapworth  (Part  II,  p.  354), 
in  which  there  is  an  equilibrium  established  between  the  dissociated 
ions  of  the  two  metallic  derivates,  or,  in  other  words,  an  equilibrium 
mixture  of  both  metallic  compounds  is  present : 

CH3 .  CO  :  CH  .  COOC2H5  +  Me     ^     CH3  .  CO .  CH .  COOC2H5  +  Me 

Me  =  metal. 

which  may  shift  from  one  side  to  the  other  according  to  the 
conditions  of  the  reaction  or  nature  of  the  reagent  or  both. 

Primarily,  no  doubt,  electrochemical  influences  prevail,  and 
determine  combinations  such  as  occur  in  the  use  of  zinc  alkyls 
and  the  Grignard  reagents.  Michael  would  probably  interpret  these 
reactions  by  supposing  the  electropositive  metal  to  link  itself  to 
oxygen  in  a  ketone,  or  to  nitrogen  in  a  cyanide,  and  by  neutralising 
the  electronegative  effect  of  oxygen  or  nitrogen  render  the  adjoining 
carbon  more  disposed  to  polymerise  (attach  itself  to  carbon),  and 
thus  attract  an  alkyl  group. 

CH3    .         .OMgBr 

=>C< 
Br       /     XJHj 

This  example  introduces  a  fourth  type  of  addition  in  which  the 
atoms  constituting  both  unsaturated  molecule  and  molecule  of 
addendum  are  dissimilar. 

Examples  of  this  type  are  very  common,   and   may  be  briefly 

1  Trans.  Chem.  Soc.,  1903,  83,  420. 


128  THE  NATURE  OF  ORGANIC  REACTIONS 

enumerated.     The  addition  products  of  aldehydes  and  Icetoncs,  C :  0, 
also  of  thialdehydes  and  thioketones,  (C :  S),  are  as  follows : 
Reagent         HCN  NH3  NaHSO,         C2H,OH  HP03 

/OH          /OH  /OH  /OH  /OH 

Product  >C<  >C/  >C<  >C/  >C/         .0 

\CN  \NH2          \SO.Na         XOC2H5         \OP^(O 

This  additive  power  of  the  CO  group  falls  away  in  something  like  the 

following  order,  depending  upon  the  nature  of  the  attached  groups : 1 

CO  CO  CO  CO  CO 

I  I         I          I         I 

CH3        C:C          RO  H2N  HO 

Similar    observations   have   been   made  by   Goldschmidt 2   on   the 
addition  of  ammonia  to  ketonic  esters. 
In  compounds  of  the  general  formula, 
R.C:O 

CH2.COOC2H5 

the  stability  of  the  additive  product  decreases  with  increasing 
positivity  of  R  in  the  following  order : 

C6H5,   COOC2H5,    CH3. 

Petrenko-Kritschenko 3  and  Stewart 4  have  shown  that  with  increasing 
negativity  of  the  neighbouring  groups  the  reactive  power  of  CO  for 
sodium  bisulphite  increases ;  with  positive  groups  it  decreases. 
The  following  percentages  were  obtained  in  thirty  minutes  with  the 
same  strength  of  solution  of  sodium  bisulphite  : 5 


Acetone          .        .         .         .47 
Methyl  ethyl  ketone      .         .25-1 
Methyl  isopropyl  ketone       .       7«5 


Piuacoline  ...  .  5-6 
Acetoacetic  ester  .  .  .  56-0 
Acetone  dicarboxylic  ester  .  61-0 


Among  other  unsaturated  organic  compounds  which  are  capable 
of  forming  additive  compounds  under  conditions,  which  have  not 
been  submitted  to  very  careful  or  systematic  examination,  are  the 
oximes  >C:NOH,  the  methyleneimides  — N:CH2,  the  azoimides 

,  the  azo-compounds  — N=N — ,  &c. 

The  next  class  of  unsaturated  compounds  to  which  attention 
will  be  directed  is  that  in  which  more  than  one  double  bond  is 
present.  This  class  may  be  subdivided  into  two  groups  :  one  in 
which  the  unsaturated  atoms  are  similar  and  adjoin  one  another, 

1  Vorlander,  Annakn,  1903,  341,  9.  2  Ber.,  1896,  29,  105. 

8  Annalen,  1905,  341,  150.  4  Trans.  Chem.  Soc.,  1905,,  87,  186. 

6  As  the  numbers  refer  to  the  quantity  formed  in  a  given  time  and  not  to  the 
reaction  velocity,  they  are  not  strictly  comparable. 


THE  KETENES,  CARBON  SUBOXIDE  129 

and  have  consequently  a  carbon  atom  in  common,  as  in  allene 
CH2:C:CH2,  and  carbon  suboxide  CO  :  C :  CO,  or  in  which  the 
unsaturated  atoms  are  different,  as  in  ketene  and  its  derivatives, 
CH2 :  C  :  0 ;  and  one  in  which  the  unsaturated  atoms  are  separated 
by  one  or  more  carbon  atoms. 

Members  of  the  allene  series  are  very  few  in  number,  and  have 
been  little  studied.  They  are  obtained  by  the  action  of  metals  on 
the  dibromo-olefines  and  removal  of  bromine  as  metallic  bromide. 

CH2:CBr.CH2Br    ->     CH2:C:CH2 

Dibromopropylene.  Allene. 

In  presence  of  sulphuric  acid  they  take  up  the  elements  of  water 
and  form  ketones,  and  further  undergo  isomeric  change,  on  heating 
with  sodium,  into  the  corresponding  acetylide, 

CH2:C:CH2    -»     CH3.C:CH 

The  Ketenes,  Carbon  Suboxide  (C.,02).  The  class  of  compounds 
known  as  ketenes  have  the  general  formula  R2C  :  CO.  They  not 
only  serve  to  illustrate  the  various  types  of  reactions  characteristic 
of  unsaturated  compounds,  but  afford  an  insight  into  the  increased 
reactivity  produced  by  the  adjoining  double  bond  on  the  ketone 
group.  The  parent  substance,  CH2-:  CO,  was  obtained  by  Wilsmore a 
by  heating  acetic  anhydride,  acetic  ester,  or  acetone  by  means  of 
a  glowing  platinum  wire,  and  by  Schmidlin  2  by  passing  the  vapour 
of  acetone  through  a  red-hot  tube. 

CH3 .  CO  .  CH.  =  CH2 :  CO  +  CH4 

Staudinger 3  obtained  various  ketene  derivatives,  such  as  methyl- 
ketene  CH3.CH:CO,  dimethylketene  (CH3)2C:CO,  phenylketene 
C(,II5CH  :  CO,  and  diphenylketene  (C6H5)2C  :  CO,  by  acting  upon  the 
halogen  acid  chloride  or  bromide  with  zinc. 

CR2C1 .  COC1  +  Zn  =  CR2  :  CO  +  ZnCl2 

Carbon  suboxide  C3O2,  which  may  be  included  in  the  same  group 
of  unsaturated  ketones,  was  obtained  by  Diels  and  Wolf 4  by  distilling 
in  i-acno  a  mixture  of  malonic  acid  or  its  ester  with  phosphorus 
pentoxide, 

CH.(COOH)2  =  CO  :  C  :  CO  +  2H2O 

or  by  acting  on  dibromomalonyl  chloride  with  zinc  filings.  Both 
ketene  and  carbon  suboxide  are  colourless  and  poisonous  gases,  with 
an  unpleasant  and  penetrating  smell.  Ketene  can  be  liquefied  at 
—  56°,  carbon  suboxide  at  7°.  Staudinger  divides  the  other  ketenes 
into  aldoketenes  of  the  formula  RCH  :  CO  and  ketoketenes  R2C  :  CO. 

1  Trans.  Chem.  Sbc.,  1907,  91,  1938.  » *£«-.,  1910,  43,  2821. 

8  Die  Ketene,  by  H.  Staudinger.     Enke,  Stuttgart,  1912. 
4  Ber..  1906,  39,  689. 

PT.  I  K 


130  THE  NATURE  OF  ORGANIC  REACTIONS 

The  former  are  colourless,  the  latter  yellow  or  orange  gases  or 
liquids.  They  are  all  extremely  reactive,  uniting  not  only  with  the 
usual  addenda  characteristic  of  ethenoid  compounds,  such  as  the 
halogen  acids  and  halogens,  forming  acid  chlorides  and  halogen  acid 
chlorides,  but  also  with  water,  alcohols,  mercaptans,  primary  and 
secondary  amines  and  acids.  In  none  of  these  reactions,  however, 
do  they  resemble  true  ketones,  but  rather  compounds  of  the  carbimide 
type  CO  :  NR. 

With  water,  ketene  and  carbon  suboxide  form  respectively  acetic 
and  malonic  acid, 

CH2  :  CO  +  H20  =  CH3  .  COOH 
CO  :  C  :  CO  +  2H2O  =  CH2(COOH)2 
With  alcohol,  they  yield  acetic  and  malonic  ester, 

CH2  :  CO  +  C2H5OH  =  CH3  .  COOC2H5 
CO  :  C  :  CO  +  2C2H5OH  =  CH2(COOC2H5)2 

With  aniline  or  ammonia,  the  ketenes  yield  anilides  or  amides, 
CH2  :  CO  +  NH2C6H5  =  CH3  .  CONHCfiH5 
(C6H5)2  :  CO  +  NH3  -  (C6H5)2CH  .  CONH2 
With  acids,  anhydrides  are  formed, 

(C6H5)2C  :  CO  +  C6H5COOH  =  (C6H5)2CH  .  CO  .  O  .  COCGH5 

/COO.COCHg 
CO  :  C  :  CO  +  2CH3COOH  =  CH2< 

XCOO  .  COCH3 

CO 


X) 

A  second  type  of  reaction  is  presented  by  the  union  of  two  or  more 
molecules  of  ketene  ;  in  other  words,  by  polymerisation.  Whilst  the 
ketoketenes  are  more  disposed  to  form  additive  compounds,  the 
aldoketenes  are  characterised  by  their  remarkable  tendency  to 
polymerise.  In  the  latter  case  polymerisation  takes  place  so  rapidly, 
even  in  dilute  solutions,  that  the  aldoketenes  cannot  be  prepared  in 
a  pure  state.  The  ketoketenes  polymerise  more  slowly,  dimethyl- 
ketene  requiring  from  one  to  two  hours  at  the  ordinary  temperature, 
whilst  diphenylketene  will  remain  unchanged  for  months.  Spon- 
taneous polymerisation,  that  is,  at  the  ordinary  temperature  and 
without  the  use  of  reagents,  leads  to  cyclobutane  derivatives  : 

R2C-CO 
2R2C:CO    ->         |      | 

OC-CR2 

A  third  type  of  reaction  is  illustrated  by  the  formation  of  an 
additive  compound  followed  by  cleavage  into  two  new  molecules. 


THE  KETENES,  CARBON  SUBOXIDE  131 

This  is  best  shown  by  the  behaviour  of  oxygen,  with  which  more 
especially  the  ketoketenes  unite.  By  passing  oxygen  into  dimethyl- 
or  diethyl-ketene  at  -20°,  white  amorphous  compounds  separate 
which  in  the  dry  state  explode  violently ;  but  suspended  in  ether 
they  break  up  into  carbon  dioxide  and  the  ketone 

R2C:CO  R2C— CO  R2C-|-CO  R2CO 

0—0  O  0-U)  C02 

II  i 

o 

The  reason  for  introducing  a  second  intermediate  dioxide  stage 
between  ketene  and  ketone  is  the  existence  of  ketene  oxides  of  the 
formula, 

R2C— CO 

v 

o 

which  in  the  case  of  phenylmethylketene  and  diphenylketene  appear 
in  considerable  quantity  along  with  the  dioxide. 

Finally,  there  is  a  fourth  type  of  reaction  illustrated  by  the  union 
of  the  ketene  with  a  second  unsaturated  molecule,  containing  one  of 
the  following  groups : 

C:C,  C:0,  C:N,  C:S,  N:0,  N:N. 

A  four-atom  ring  is  first  produced,  which  more  or  less  easily  breaks 
down  into  two  new  molecules. 

With  ketones,  for  example,  the  following  reaction  takes  place : 

R2C :  CO      R2C4-CO  R2C 

=     I  II     ->      II  +co2 

R2C:0        R2C-j-O  R2C 

The  addition  may  occur  in  two  ways,  and  it  has  actually  been 
observed  in  the  case  of  the  compounds  with  the  carbimides  thus  : 
R2C:CO  R2C:CO 

R2C:NR  RN:CR2 

R2C— CO  R2C— CO 

II  I      i 

R2C— NR  RN— CR2 

Where  union  with  nitroso  compounds  occurs,  such  as  diphenyl- 
ketene with  nitrosobenzene,  combination  and  cleavage  follow  two 
directions : 

K  2 


132  THE  NATUEE  OF  ORGANIC  REACTIONS 

(C6H5)2C-CO  (C6H5)2C      CO 

0-NCGH5  O     NC6H5 

(C6H5)2C-CO  (C0H5)2C      CO 

I  '   I        -*  11  +  11 

CGH5N-0  C6H5N      O 

Thus  every  type  of  reaction  is  represented,  and  it  should  be 
observed  that  in  addition  to  the  foregoing,  additive  compounds 
are  formed  with  pyridine  and  quinoline,  acid  chlorides,  hydrogen 
cyanide,  and  the  Grignard  reagent,  yet  in  no  case  is  the  behaviour 
that  of  a  true  ketone.  This  difference  in  character  may  be  ascribed 
to  the  presence  of  two  adjoining  double  bonds,  which  not  only 
enhance  the  reactivity  of  the  molecule,  but  fundamentally  alter  the 
ketonic  character  of  the  substance. 


Nl       |C(CH3)2 

ocl    Jco 

C(CH3)2 

Dimethylketene-pyridine. 
A  group  of  compounds  termed  ketimines  of  the  general  formulae 

R.CH:NH      R.CRI:NH 

have  more  recently  been  obtained  by  Moureu  and  Mignonac  *  by  the 
action  of  ammonium  chloride  on  the  product  of  the  action  of  the 
Grignard  reagent  on  the  nitriles 

R .  C( :  NMgBrJRi  +  NH4C1  =  RR:C  :  NH  +  MgClBr  +  NH3 
They  are  low-boiling  basic  substances  which  combine  with  acids 
forming  crystalline  salts,    readily   decomposed   by  water  into  the 
ketone  and  ammonium  chloride 

RRjC  :  NH2C1  +  H2O  =  RRXCO  +  NH4C1 

Conjugated  Double  Bonds.  This  term  has  been  applied  to  those 
unsaturated  compounds  in  which  the  unsatu rated  groups  have  no 
single  carbon  atom  in  common,  but  the  pairs  of  double  bonds  are 
separated  as  in  isoprene  or  butadiene,  acrolein  or  glyoxal. 

CH2 :  C(CH3) .  CH :  CH2       CH2 :  CH .  CH  :  CH2        CH2 :  CH .  CH  :  0 

Isoprene.  Butadiene.  Acrolein. 

0:CH.CH:0 

Glyoxal. 

*  Comp.  rend.,  1913,  156,  1801. 


CONJUGATED  DOUBLE  BONDS  133 

Under  certain  conditions  of  atomic  environment  such  a  grouping  of 
double  bonds  exhibits  abnormal  chemical  behaviour  and  abnormal 
physical  properties.  For  example,  muconic  acid  on  reduction  or 
bromination  does  not  unite  with  four  atoms  of  each  element,  as  the 
existence  of  two  pairs  of  double  bonds  might  lead  one  to  expect,  but 
only  two  atoms  are  absorbed,  and  attach  themselves  to  the  a  carbon 
atoms  at  either  end  of  the  chain,  a  process  which  is  accompanied  by 
a  shifting  of  the  double  bond  to  the  middle  position.1 

HOOC  .  CH  :  CH  .  CH  :  CH  .  COOH 

Muconic  acid. 
H3  Br, 

S  \ 

HOOC  .  CH  ,  .  CH  :  CH  .  CH2  .  COOH        HOOC  .  CHBr  .  CH  :  CH  .  CHBr  .  COOH 

Hydrouiuconic  acid.  Muconic  acid  dibromide. 

Similarly,  diphenylbutadiene  unites  with  nitrogen  tetroxide  to  form 
a  1  .  4  dinitro  compound.' 

CGH3CH  :  CH  .  CH  :  CH  .  C6H-,  +  N2O4 

=  CGH5CH(NOJ  .  CH  :  CH  .  CH(NOJC6H5. 

That  the  positive  hydrogen  atoms  should  seek  the  most  negative 
carbon  atoms  is  not  surprising,  and  these  are  situated  at  the  end  of 
the  chain  ;  but  that  the  negative  bromine  atoms  and  nitro  groups 
should  act  similarly  introduces  a  difficulty  for  which  an  electro- 
chemical explanation  seems  insufficient.  Moreover,  there  is  no 
apparent  reason  why,  supposing  the  first  two  atoms  to  enter  the  end 
positions  in  the  chain,  reduction  or  bromination  should  stop,  as 
it  does. 

Thiele's  Theory.  To  account  for  this  and  similar  phenomena 
J.  Thiele3  has  introduced  his  theory  of  partial  valencies. 

According  to  Thiele  the  valency  of  unsaturated  atoms,  which  are 
usually  denoted  by  double  or  treble  linkages,  is  not  wholly  utilized, 
but  some  force  of  affinity  remains  as  a  residual  or  partial  valency,  by 
virtue  of  which  the  process  of  addition  is  initiated.  'These  partial 
valencies  are  indicated  by  dotted  lines. 

C=C  C=0  C=N  N=N 


Ethylene,  for  example,  attaches  bromine  in  the  first  instance  by 
its  partial  valencies,  which  change  to  a  full  valency  simultaneously 
with  the  appearance  of  a  single  linkage  in  place  of  the  double  bond. 

1  Annalen,  1883,  216,  171  ;  1885,  227,  46  ;  1889,  251,  257  ;  1890,  256,  1. 

2  Straus,  Ber.,  1909,  42,  2300.  3  Annalen,  1899.  306,  87. 


134  THE  NATURE  OF  ORGANIC  REACTIONS 

H2C  •  H2C--Br  H2CBr 

||       +  BT,    -*          ||  ->        "| 

H2C  .....  H2C-Br  H2CBr 

The  electrochemical  nature  of  the  elements  determines  the  process 
of  addition  ;  for  example,  N=N  has  no  affinity  for  chlorine  and  no 
addition  of  this  element  occurs  ;  hydrogen  unites  with  oxygen  rather 
than  with  carbon,  the  acid  radical  with  carbon  rather  than  with 
hydrogen,  and  so  forth. 

The  existence  of  residual  affinity  in  unsaturated  atoms  agrees  with 
Thomsen's1  calculation  of  the  thermal  value  of  an  ethylene  bond, 
which  he  finds  less  than  that  of  two  single  linkages. 

Passing  to  the  case  of  two  adjoining  pairs  of  double  linkages 
referred  to  at  the  beginning  of  this  section,  Thiele  supposes  the  central 
pair  of  partial  valencies  to  neutralize  one  another  and  lose  their  activity 
like  the  opposite  poles  of  two  magnets  when  made  to  touch.  The 
union  is  indicated  by  a  curved  line  and  is  termed  conjugated,  and  the 
whole  arrangement  a  conjugated  double  lond.  In  this  way  the  partial 
valencies  of  only  the  end  atoms  remain  active  and  capable  of 
attaching  new  atoms,  whilst  the  conjugated  atoms  are  inactive. 

=C    ->    C=C—  C=C 


Compounds  with  conjugated  double  bonds  are  therefore  more 
saturated  and,  as  we  shall  see  later  (Part  II,  p.  67),  have  a  smaller  heat 
of  combustion*'  The  same  thing  is  supposed  to  occur  in  unsaturated 
ketones  and  in  diketones  and  acids. 

c=c         o=c—  c=o 


As  soon  as  addition  has  taken  place  the  conjugated  bond  changes 
into  a  normal  double  bond,  and  in  this  way  reduction  or  bromination 
of  the  end  carbon  atoms  is  effected. 

The  following  are  a  few  examples.  Phenylcinnamylacrylic  acid 
gives  on  reduction  and  bromination  the  1  .  4  dihydro  and  dibromo 
acid  respectively.2 

C6H5CH2  .  CH  :  CH  .  CH(C6H5)  .  COOH 


C6H5CH  :  CH  .  CH  :  C(CCH5)  . 

C6H5  .  CHBr  .  CH  :  CH  .  CBr(C0H5)  .  COOH 
The  aft  unsaturated  acids  with  the  conjugated  grouping 

1  Zeit.physik.  Chem.,  1887,  1,  369.  2  Annalm,  1899,  300,  201. 


THIELE'p  THEORY  135 

RClt=CH  .  6=0 

^1 
OH 

do  not  unite  with  bromino  as  readily  or  as  rapidly  as  the  fiy  acids 
RCH=CH.CH2.C==  O 

,  which  are  imconjugated  and  therefore  less 
OH 

saturated.  The  rate  of  hydration  of  saturated  and  unsaturated  an- 
hydrides shows  great  differences,  which  are  ascribed  to  conjugation. 
Maleic  -*acid,  which  contains  conjugated  double  bonds,  undergoes 
hydration  ten  times  as  quickly  as  succinic  anhydride.1 

CH2-< 


According  to   Thiele's  theory  benzil   should   give  on  reduction 
diphenylethylene  glycol,  whereas  benzoin  is  actually  formed. 
H5C6     C6H5      sh^uld         H5C6     C6H5        ^ut        H5C6     C6H5 

O=C  —  C=0       glve       HO.C=C.OH    glves    0=C  —  CHOH 

Benzil.  Diphenylethylene  glycol.  Benzoin. 

How  is  this  to  be  explained  ?  Thiele  attributes  the  final  stage  to 
isomeric  change  of  the  very  labile  intermediate  product.  Supposing, 
however,  reduction  to  be  effected  in  presence  of  acetic  anhydride 
and  sulphuric  acid,  the  acetyl  derivative  of  the  intermediate  glycol 
should  be  formed  and  isomeric  change  arrested.  This  is  precisely 
what  happens.  Two  stereoisomeric  diacetates  of  diphenylethylene 
glycol  are  formed. 

H5C6     C6H5 

CH3CO  .  OC=CO  .  COCH3 

Similarly,  benzylidene  acetone  should  give  hydrocinnamyl  methyl 
ketone  in  place  of  the  unstable  alcohol. 

CH3  CH3 

M    I  I 

C0H5.CH=0-C=0    -»    C6H5.CH2.CH=C-OH    -> 

C6H5CH2.CH2.CO.CH3 
But  Harries  finds  that   the  reaction  proceeds  otherwise,  and  that 

1  Rivett  and  Sidgwick,  Trans.,  1910,  97,  1677. 


136  THE  NATURE  OF  ORGANIC  REACTIONS 

two  molecules  of  benzylidene  acetone  join  up  to  form  a  saturated 
double  ketone. 

CH  CH     C6H5 


1 

1 

| 

CH 

CH- 

-CH 

II 

->          I 

1 

CH 

CH2 

CH2 

Jo- 

•      CH3  .  CO 

I 
CO  .  CH3 

CH, 

The  reaction  is  explained  by  supposing  that  the  electronegative 
oxygen  £rst  unites  with  hydrogen,  and  the  alcohol  thus  formed 
isomerises  to  the  ketone  form.  This  leaves  the  partial  valencies  of 
the  carbon  free  to  unite  with  hydrogen  or  with  a  second  molecule, 
and  it  is  the  latter  process  which  occurs. 

The  reduction  of  niuconic  acid  is  also  readily  explained.  As  it 
contains  three  conjugated  linkages  only  the  end  oxygen  atoms 

,OH 
possess  partial  valencies  and  the  end  groups  C<          isomerise  to 

X)H 
carboxyl  by  passing  on  an  atom  of  hydrogen  to  the  a  carbon. 

OH  OH 

H=CH—  CH—CH—  C=0 


=C—  C 


Muconic  acid. 

HOV  /OH 

>C—  CH=CH—  CH=CH-  C< 
HO/  ^  ^    \OH 

Intermediate  form. 

OH  OH 


O=C— CH2— CH=CH—  CH2 .  C^O 

Hydromuconic  acid. 

The  theory  explains,  moreover,  in  a  simple  fashion  why  fumaric 
acid  is  more  easily  reduced  than  crotonic  acid,  since  electropositive 
oxygen  attaches  hydrogen  more  readily  than  carbon. 

OH  OH  CH3  OH 

I  III 

O^C-CH=-CH— 0=0  CH—CH— C=-0 


Fumaric  acid.  Crotonic  acid. 

This  may  also  explain  why  the  halogen  enters  the  (3  position,  where 
halogen  acid  combines  with  an  unsaturated  acid.     In  acrylic  acid, 


THIELE'S  THEORY  137 

for  example,  the  hydrogen  attaches  itself  to  oxygen  and  the  bromine 
to  carbon. 

OH 

I  /OH 

CH2=CH—  C=0  -»  CH2-CH=C<          -*  CH2Br.CH2.CO.OH 
j  ^      j  \OH 

Acrylic  acid.  Br  /3-Bromopropionic  acid. 

In  the  same  way,  when  addition  of  water  or  ammonia  takes  place, 
OH  and  NH2  unite  with  the  /3  carbon  and  hydrogen  to  the  a  carbon. 
It  is  not  therefore  due  to  the  negative  addendum  being  repelled  by 
the  negative  carboxyl  group,  as  frequently  assumed.  Ammonia  com- 
bines with  phorone  thus  : 


3X 

>C:CH-CO.CH:C<          ->          >C—  CH2-CO.CH: 
CH/  \CH3       CH/I 

Phorone.  NH2 

Thiele's  theory  also  explains  the  addition  of  magnesium  acyl  or 
alkyl  bromide  to  unsaturated  ketones  and  esters  ;  but  the  position 
taken  by  the  radical  is  here  found  to  depend  on  the  nature  of  the 
radical  already  associated  with  the  ketone  or  ester  group.  In  the 
case  of  cinnamic  ester,  a  phenyl  or  cyanogen  group  attached  to  the 
a  carbon  will  cause  the  acyl  group  to  attach  itself  to  the  ft  carbon,  in 
the  case  of  a  methyl  group  to  the  a  carbon.1 

Crossed  Double  Bonds.     An  example  of  what  are  termed  crossed 
double  bonds  occurs  in  dibenzalpropionic  acid. 
1234 

C6H5CH=C-CH=CH.  C6H- 


OH 

Here  it  will  be  observed  that  a  conjugated  system  may  be  formed 
between  the  different  pairs  of  carbon  atoms. 


=CH  .  C6H5 

(1 


OH 

Such  an  arrangement  presents  two  alternative  ways  in  which  addition 

may  occur,  the  nature  of  the  product   depending   on  that  of  the 

1  Kohler,  Amer.  Chem.  Journ.,  1905,  36,  529  ;  1906,  37,  369  ;  1907,  38,  611. 


138  THE  NATURE  OF  ORGANIC  REACTIONS 

addendum*  In  the  case  of  bromine  it  is  scarcely  surprising  to  find 
that  it  attaches  itself  to  carbon  atoms  1,  4.  Hydrogen  and  halogen 
acid,  on  the  other  hand,  distribute  themselves  between  oxygen  and 
the  nearest  carbon  atom.  With  hydrogen  the  following  compound 
is  formed  : 

C6H5  .  CH2  .  CH  .  CH=CH  .  CGH5 

COOH 

It  should,  however,  be  pointed  out  that  in  addition  to  the  1  .  4 
dibromo-additive  compound,  a  second,  3  .  4,  compound  is  also 
produced.  How  is  the  latter  accounted  for  ?  Thiele  lays  emphasis 
on  the  fact  that  the  partial  valency  of  the  central  carbon,  2,  by 
being  distributed  between  its  two  neighbours,  does  not  neutralise 
their  activity,  and  some  is  available  for  additive  purposes.  Hence 
the  dibromo  derivative  appears  : 

CGH-  .  CH  :  C  .  CHBr  .  CHBr  .  CCH, 

COOH 

Borsche  l  has  recently  shown  that  the  union  of  ethyl  acetoacetate 
with  certain  ketones  containing  a  system  of  crossed  double  linkages 
O 

depends  on  the  length  of  the  chain.      If  the  chain  fs 
CiC.C.C 

sufficiently  long  the  ends  may  approach  one  another  so  closely  that 
a  part  of  the  residual  affinity  is  saturated,  and  will  not  unite  with 
the  ester.  This  is  the  case  with  dicinnamylidene  acetone,  but  not 
with  distyryl  ketone. 

C6H56H    CHC6H5  CCH5CH      CH.C6H5 

II        II 
HC  O  CH 


HC        C        bH 

HOC 


CH     CH 

Sufficient  has  been  said  to  indicate  the  general  nature  of  the 
theory,  and  the  resources  available  for  meeting  apparent  anomalies. 
Before  discussing  the  exceptions  to  the  theory,  it  may  be  well  to 
consider  its  application  to  the  aromatic  series  of  compounds.  Its 
application  to  the  benzene  formula  is  fully  discussed  (Part  II, 
chap,  vii),  and  little  more  need  be  said  on  the  subject.  In  refer- 
ence to  it  Thiele  says  :  '  as  by  the  neutralisation  of  the  partial 
valencies  the  original  three  double  bonds  vanish,  no  distinction  can 
be  drawn  between  them  and  the  secondary  (conjugated)  double 
bonds.  Benzene  contains  six  inactive  double  bonds.  Thus,  the 
difficulty  presented  by  the  two  ortho  positions,  1  .  2  and  1  .  6;  which 

1  Annaltn*  1910,  375,  145. 


CROSSED  DOUBLE  BONDS  139 

Kekule  attempted  to  meet  by  the  aid  of  his  dynamic  hypothesis, 
disappears.     Benzene  may  be,  therefore,  represented  by  the  formula, 

H 

C 

HC/\CH 

H 

0 
H 

if  it  is  desired  to  attach  weight  to  its  saturated  character  and  to  the 
equality  of  the  ortho  positions.' 

Thiele  has  applied  the  theory  in  a  variety  of  ways  to  explain 
certain  characteristics  of  benzene  derivatives.  Phenol,  for  example, 
is  distinguished  by  its  high  reactivity,  which  it  loses  to  some  extent 
in  its  ethers  and  esters.1  Assuming  that  it  may  react  in  its  isomeric 
form  of  ketone,  the  partial  valencies  will  at  once  come  into  play. 

O- 


The  reduction  of  the  aromatic  acids  (see  Part  II,  p.  397)  may  be 
considered  from  the  same  point  of  view  as  that  of  muconic  acid 
(p.  133).  On  the  reduction  of  terephthalic  and  phthalic  acids,  the 
hydrogen  attaches  itself  to  the  a  carbon  atoms. 


OH 
| 


X)H 
OH 

Reduction  of  Phthalie  acid. 

1  That  the  phenols  show  greater  reactivity  than  their  ethers,  and  that  they 
react  in  the  ketone  rather  than  in  the  enol  form,  has  been  questioned.  K.  H. 
Meyer  and,Lenhardt,  Annalen,  1913,  398,  66. 


HO 


THE  NATURE  OF  ORGANIC  REACTIONS 


H0-C=0 

I) 


HO-C-OH 


H     COOH 
\/ 


/ 

HO— C=Q—  HO-C— OH  H     COOH 

Eduction  of  Terephthalic  acid. 

The  quinones  furnish  an  interesting  case,    because   addition   may 
occur  in  different  positions,  and  the  differences  observed   may   be 
ascribed  to  the  nature  of  the  entrant  atoms  and  groups. 
O  •• 


A,.. 


Yt: 


o 

p-Quinone.  o-Quinone. 

Hydrogen  attaches  itself  to  oxygen,  and  quinol  and  catechol  result. 
OH 


— OH 


OH 


That  red  uction  is  arrested  at  this  stage  naturally  follows.  Halogens, 
on  the  other  hand,  will  seek  the  carbon  atoms,  and  di-  and  tetra- 
chloroquinones  will  be  formed.  Halogen  acid  will  distribute  itself 
between  the  oxygen  and  the  nuclear  carbon,  and,  according  to  Thiele, 
will  pursue  the  following  course  : 

0— •  OH  OH 


VNa 


L 


0   -  O   -  OH 

The  quinonimines  will  act  in  a  similar  fashion.  Quinonediimine 
on  reduction  should  produce  ^-phenylenediamine,  whilst  sulphurous 
acid  should  react  like  hydrogen  chloride,  the  acid  group  remaining 


CROSSED  DOUBLE  BONDS  141 

attached  to  the  nucleus,  and   the  hydrogen  passing  to  the  imino 
group. 

NH2  NH 

i  II 

x\ 


NH2  NH  NH 

Meisenheimer1  has  utilized  the  idea  of  partial  valencies  in  order  to 
explain  certain  reactions  of  nitro  compounds,  such,  for  example,  as 
the  formation  of  alkali  salts  of  trinitrobenzene  and  trinitrotoluene  in 
alcoholic  solution,  and  their  combinations  with  potassium  cyanide. 

H     OCH3  H     CN 

s./ 


1=0 

I 
OK 

In  naphthalene  the  distribution   of    partial    valencies    and    their 
conjugation  will  appear  as  follows  : 


'•  :         I 

The  partial  valencies  of  the  two  central  carbon  atoms  will  not 
suffice  to  neutralise  those  in  the  a  positions,  and  consequently  they 
are  the  most  easily  attacked  ;  for  it  is  well  known  that  substitution 
takes  place  in  these  positions.  Supposing  that  on  reduction  hydrogen 
enters  positions  1 .  4,  what  will  be  the  effect  ?  The  half  partial 
valencies  of  the  two  central  carbon  atoms  will  be  withdrawn  from 
this  pair,  and  consequently  those  directed  towards  5.8  willbe/w?Z 
partial  valencies,  or,  in  other  words,  the  unreduced  ring  will  be  trans- 
formed into  a  true  benzene  ring,  whilst  the  other  ring  can  take  up 
two  further  hydrogen  atoms,  as  Bamberger  has  found  (Part  III,  p.  283). 

Annakn,  1902,  323,  219,  241. 


142  THE  NATURE  OF  ORGANIC  REACTIONS 


)  I  I...  - 1) 

vy    '  . 

Anthracene  in  the  same  way  may  be  represented  by  the  formula 


Thiele  claims  for  this  formula  the  advantage  that  it  explains  the 
well-known  reactivity  of  the  para-carbon  atoms  of  the  central 
nucleus,  a  view  which  has  been  developed  by  Meisenheimer  l  in 
relation  to  the  nitro-derivatives.2 
Phenanthrene  has  the  formula, 


HC      CH 

which  explains  the  peculiar  reactivity  of  the  HC=CH  group. 

The  effect  of  conjugation  is  not  manifested  only  by  chemical 
behaviour,  but  is  seen  in  the  enhanced  optical  activity,  magnetic 
rotation,  and  refractivity  described  in  Part  II,  pp.  28,  53,  and  228. 

An  interesting  extension  of  Thiele's  theory  has  been  brought  for- 
ward by  Robinson  and  Hamilton.3  From  their  own  and  Decker's 
observations4  they  conclude  that  tervalent  nitrogen  may  act  as  a 
member  of  a  conjugated  system.  They  have  been  able  to  show  that 
where  the  group 

R2C  =  C-NR2        (R2  =  alkyl  or  H) 

occurs,  whether  the  nitrogen  forms  part  of  a  chain  or  ring,  both 
alkyl  salts  (alkyl  acid  sulphates  and  alkyl  iodides)  attach  themselves 
to  the  end  atoms,  the  alkyl  group  (R)  joining  the  carbon  atom  and 
the  negative  group  (K)  the  nitrogen  with  the  usual  change  of  linkage 

R2C—  C  =  NR2 

R  X 

This  may  take  the  form  of  direct  addition  or  lead  to  a  secondary 
process  of  hydrolysis,  as  illustrated  by  the  behaviour  of  /?«diethyl- 

1  Annalen,  1902,  323,  204. 

2  It  should  be  pointed  out  that,  though  there  may  be  more  free  valency  at 
the  disposal  of  the  two  central  carbon  atoms,  the  para-carbon  atoms  in  the  two 
side  rings  are  in  a  condition  precisely  similar  to  those  in  the  o  positions  in 
naphthalene. 

8  Trans.  Chem.  Soc.,  1916,  109,  1029,  1033.     «  Ber.,  1904,  37,  523  ;  1905,  38,  2893. 


CROSSED  DOUBLE  BONDS  143 

aminocrotonic   ester  with  alkyl  iodides  giving,  by  hydrolysis  with 
water,  methylacetoacetic  ester. 

The  action  is  explained  as  follows  : 

CH3I 

(C2H5)2N  .  C(CH3)  :  CH  .  CO,R    -> 


IN(C2H5)2  .  C(CHo)  .  CH(CH3)  .  CO2R    -> 

0  :  C(CH3)  .  CHCH3  .  CO2R  +  NH2(C2H5)2I 

To  explain  the  behaviour  of  nitrogen  in  this  addition  process,  the 
authors  consider  that  it  possesses  (in  addition  to  two  latent  valencies) 
two  partial  valencies,  and  that  the  normal  valency  of  every  atom  may 
be  accompanied  by  a  partial  valency.  They  deduce  a  number  of 
interesting  results  from  this  theory,  and  suggest  that  oxygen  possesses 
partial  valencies,  thus  explaining  the  formation  of  alkyl  derivatives 
of  acetoacetic  ester  by  the  attachment  of  iodine  of  the  alkyl  iodide  to 
oxygen  and  the  methyl  group  to  carbon  of  the  sodium  compound. 

Like  most  chemical  theories,  that  of  Thiele  has  become  an 
attractive  target  for  the  shafts  of  criticism.  It  has  been  attacked  by 
Michael.  Hinrichsen,  Erlenmeyer,  and  others  on  the  ground  that  it 
is  not  only  unnecessary,  but  that  the  numerous  exceptions  which 
have  been  observed  render  it  untenable.  Michael  l  accuses  its  author 
of  adopting  or  discarding,  as  may  suit  his  purpose,  the  positive- 
negative  rule  (see  p.  113).  He  points  out  that  Thiele  assumes  that 
in  certain  cases  the  atoms  or  groups  of  the  addendum  distribute 
themselves  according  to  their  electrochemical  character,  but  that  the 
addition  of  halogen  acids  and  ammonia  to  unsaturated  acids  is  based 
on  an  entirely  different  conception.  Again,  in  dibenzalpropionic 
acid  (p.  137),  the  two  carbon  atoms  with  the  strongest  partial 
valencies  are  1  .  4,  and  consequently  the  1  .  4  dibromo  acid  should 
of  the  two  be  formed  in  larger  quantity,  whereas  the  1  .  2  dibromo 
compound  predominates.  These  and  other  additive  processes  find, 
according  to  Michael,  a  readier  explanation  by  the  aid  of  the  positive- 
negative  rule.  Hinrichsen,2  like  Michael,  assails  the  theory  on  the 
ground  that  it  attaches  too  little  weight  to  the  electrochemical 
nature  of  the  additive  process  ;  *  the  constitution  of  a  substance 
produced  by  the  addition  of  atoms  and  radicals  to  unsaturated 
compounds  is  determined  in  the  first  place  by  the  qualitative 
relationship  existing  between  the  addendum  on  the  one  hand  and 
the  atoms  or  atomic  groups  present  in  the  unsaturated  molecule  on 
the  other.'  Among  the  many  exceptions  to  Thiele's  theory  the 
following  may  be  cited  : 

i  J.  PraM.  Chem.,  1899,  60,  467.  2  Annalen,  1904,  336,  174. 


144  THE   NATURE   OF  ORGANIC  REACTIONS 

Michael's  reaction  (p.  202)  and  the  addition  of  sodium  malonic 
ester  to  cinnamylacrylic  ester,1 

C6H5CH  :  CH  .  CH  :  CH  .  COOC2H5          C6H6CH  :  CH  .  CH  .  CHNa  .  COOC2H5 

+  NaCH(COOC2H5)2  CH(COOC2H5)2 

the  addition  of  bromine  to  cinnamic  acid,  which  follows  the  normal 
course,  the  reduction  of  cinnamylformic  acid  to  phenyl-a-hydroxy- 
isocrotonic  acid,2 

C6H5CH:CH.CO.COOH    -»    C6H5CH  :  CH  .  CH(OH)  .  COOH, 
the  addition  of  hydrogen  cyanide  and  magnesium  methyl  iodide  to 
the  CO  group  of  cinnamic  aldehyde,3 

/OH  /OMgl 

C6H5CH  :  CH  .  CH<  C6H5  .  CH  :  CH  .  CH< 

X5N  XCH3 

the  addition  of  bromine  to  diphenylbutadiene  4  and  to  cinnamylidene- 
malonic  ester,  both  of  which  yield  1  .  2  dibromides, 

C6H5CHBr  .  CHBr  .  CH  :  CH  .  C6H5, 
C6H5CHBr  .  CHBr.  CH  :  C(COOC2H5)2, 

and  the  reduction  of  dibenzalpropionic  acid,  which  also  gives  a  1  .  2 
dihydro  derivative, 

CGH5CH  :  CH  .  CH(C02H)  .  CH2  .  C6H5. 

Apparent  exceptions  in  the  case  of  1  .  2  additive  compounds  of 
unsaturated  ketones  and  esters  with  ammonia,6  hydroxylamine,6 
hydrogen  cyanide,7  and  sulphurous  acid  8  may  be  explained  on 
Thiele's  theory  by  including  the  CO  of  the  carboxyl  group  in  tho 
conjugated  series,  and  assuming  isomeric  changes  to  follow  thus  : 


=C-0  ->  >C—  CH-C=0 

I  II 

NHOH       H          NHOH 

=C—  0  ->  >C—  CH—  C=0  &c. 

I'll 
CN  H  CN 

1  Vorlander,  Ber.,  1903,  36,  2339. 

2  Erlenmeyer,  jun.,  Ber.,  1903,  36,  2529  ;  1904,  37,  1318. 

8  Kohler,  Am.  Otem.  J.,  1904,  31,  642  ;  1905,  33,  153,  333  ;  1907,  36,  520. 
4  Straus,  Ber.,  1909,  42,  2866  ;  Riiber,  Ber.,  1911,  44,  2974. 
6  Koehl  and  Dinter,  Ber.,  1903,  36,  172. 

6  Harries,  Ber.,  1897,  30,  230;  1904,  37,  252.     Posner,  Ber.,  1903,  36,  4305; 
1907,  40,  218,  227  ;  1909,  42,  2785.     Riedel  and  Schulz,  Annalen,  1909,  367,  14. 

7  Lapworth,  Trans.  Chem.  Soc.,  1903,  83,  995;  1904,  85,  1214.     Knoevenagel, 
Ber.,  1904,  37,  4065. 

8  Tiemann,  Ber.,  1898,  31,  3297  ;  Knoevenagel,  Ber.,  1901,  37,  403S. 


THIELE'S  THEORY  145 

Thiele  and  Meisenheimer,1   who  obtained  the  hydrogen  cyanide 
compound  of  cinnamylidene  malonic  ester, 

C6H5CH :  CH .  CH .  C(COOC2H5)2 

CN 


i 


admitted  that  it  constituted  an  exception  to  the  theory,  and,  if  this 
is  so,  others  may  be  included  in  the  same  category. 

Hinrichsen 2  has  formulated  the  additive  process  on  the  basis  of 
Michael's  positive-negative  rule  in  the  following  series  of  simple 
propositions : 

Addition  is  determined  by  the  electrochemical  nature  of  the 
unsaturated  groups  as  well  as  by  that  of  the  constituents  of  the 
addendum.  If  the  latter  are  of  opposite  polar  character,  as  H  .  Br, 
H.CN,  K.HS03,  H.NH2,,  Na . HC(COOC.H5)2 ,  Na.OC2H5, 
C6H5CH2S  .  H,  H .  NHOH,  the  mutual  attraction  of  the  constituent 
atoms  or  groups  will  direct  them  to  adjoining  atoms,  ie.  to  the 
1 .  2  position.  If,  on  the  other  hand,  the  constituents  of  the 
addendum  are  the  same,  H2,  Br2,  N2O4,  two  conditions  may  obtain ; 
either  mutual  repulsion  may  drive  them  apart  into  positions  1  . 4, 
or  the  opposite  polar  character  of  the  unsaturated  groups  may 
counteract  the  mutual  repulsion  of  the  constituents  of  the  addendum, 
and  cause  the  latter  to  enter  positions  1.2,  as  in  cinnamylidene 
malonic  ester, 

C6H5CH  :  CH .  CH  :  C(COOC2H5)2  +  Br2  = 

C6H5CHBr .  CHBr  .  CH  :  C(COOC2H5)2. 

If,  finally,  each  unsaturated  group  in  position  1 .  2  is  oppositely 
polar  to  each  constituent  of  the  addendum,  the  mutual  attraction 
may  cause  the  latter  to  enter  positions  1 .  2  instead  of  driving  them 
apart.  Thus,  on  reducing  dibenzalpropionic  acid,  the  two  positive 
hydrogen  atoms  are  attracted  to  the  two  negative  groups  in 
positions  1 .  2, 

C6H5CH  :  CH  .  C(C02H) :  CH  .  C6H5    -> 

C6H5CH  :  CH  .  CH(CO2H) .  CH2 .  C6H5. 

The  addition  in  positions  1 .  4  generally  occurs  under  special 
conditions.  Erlenmeyer,  jun.,3  like  Hinrichsen,  considers  that  the 
principle  of  free  valencies  in  the  case  of  unsaturated  compounds 
serves  the  purpose  better  than  that  of  Thiele's  partial  valencies,  and 
that  the  union  of  ethylene  and  bromine  may  be  expressed  thus  : 

1  Annalen,  1899,  308,  247.  a  Chem.  Ztg.,  1909,  33,  1097. 

3  Annaltn,  1901,  316,  43. 

PT   J  I. 


146          THE   NATURE  OF  ORGANIC  REACTIONS 
H2C-  H2C— Br 

H2C-  ~  H2C-Br 

He  adopts  Kekule's  view  (p.  110)  that  addition  must  be  assumed  to 
precede  substitution  in  saturated  compounds,  and  therefore  the  theory 
of  partial  valencies  must  logically  be  extended  to  them  also.  Thiele's 
theory  must  consequently  either  be  discarded  or  expanded.  KekulS's 
scheme  does  not,  however,  include  all  reactions,  and  to  extend  its 
scope  Erlenmeyer  has  added  the  following : 

f 

\ 

/* 

c  c  c 

which  is  intended  to  convey  the  notion  of  the  mechanism  of  the 
interaction  of  three  reacting  groups  before,  during,  and  after 
a  reaction,  as,  for  example,  the  formation  of  ethane  from  methyl 
iodide  and  sodium, 

I  I 

CH 


,N 
' 


3,      'Na  , 

I  I 


or  the  polymerisation  of  acetaldehyde  and  acetylene, 
0  O 

.CH.CH,          CH,.CH/\CH.CH 


CH  CH 

CH3 

CH  CH 

CH      HCf  ^CH 


AE 


CH^,  'CH      Hcl  ,CH 
CH  CH 

The  idea  may  be  applied  to  the  reduction  of  benzil  and  muconic  acid, 
when  Thiele's  theory  becomes  unnecessary. 


THIELE'S   THEORY  147 

COOH  COOH 

OH  CH  CH2 


H  _^   <W 

II 

'H          CH'J 


CcH5  .  v^         XA  ^6^5  •  ^NV 

OH  CH  CHL 

COOH  COOH 

According  to  Erlenmeyer  this  view  of  the  process  has  the 
advantage  over  Thiele's,  inasmuch  as  it  is  of  general  application, 
and  presents  a  variety  of  reactions  from  a  common  standpoint, 
without  recourse  to  hypothetical  partial  valencies.  His  further 
attempts,  like  those  of  Knoevenagel,1  to  represent  the  various  kinds 
of  chemical  combination  by  phases  in  the  oscillation  of  carbon 
tetrahedra  or  spheres  cannot  be  regarded  as  very  convincing,  and 
must  be  left  to  the  reader  for  reference. 

An  interesting  view  of  the  nature  of  the  addition  process,  as  it 
occurs  in  unsaturated  ketones,  has  been  described  by  Vorlander  and  his 
collaborators *  from  results  of  observations  by  themselves  and  others 
on  the  action  of  acids  (hydrochloric,  hydrobromic,  sulphuric,  phos- 
phoric, and  picric  acids)  and  a  few  halide  salts  (HgCl2,  FeCl3)  on 
certain  aromatic  a/?  unsaturated  ketones  containing  the  group 
C :  C .  C  :  O.  They  find,  for  example,  that  substances  such  as 
dibenzalacetone,  CCH5CH  :  CH  .  CO .  CH  :  CH .  C6H5  the  correspond- 
ing dianisalacetone,  &c.,  form  additive  compounds  with  one  or  two 
molecules  of  hydrogen  chloride  or  bromide,  or  one  molecule  of 
sulphuric  acid ;  that  benzalacetone,  C6H5CH  :  CH.  CO .  CH3,  unites 
with  one  molecule  of  hydrogen  chloride,  and  so  forth.  This  reaction 
appears  to  take  place  in  two  well-marked  phases.  In  the  first  phase, 
an  unstable  and  brightly  coloured  yellow,  orange,  or  red  compound 
called  A  is  formed,  which,  on  the  addition  of  water,  easily  loses  acid 
and  gives  the  original  compound  ;  in  the  second  phase  the  colour 
vanishes  more  or  less  quickly  with  the  production  of  a  stable, 
colourless  compound,  B.  The  authors  then  discuss  the  nature  of 
the  change.  They  discard  in  turn  the  theory  of  Kehrmann  and 
Wentzel,  who  ascribe  to  A  and  B  a  different  structure, 

OH  Cl     H 

Cl\      s=\  j v 

>C<           >C:CH.CH:C.R        Hvf          >C.  CH.CH.  CO.  R 
jj/     \=— =/  \ / 

A  (coloured).  B  (colourless). 

1  Annalen,  1900,  311.  203. 

8  Ber.,  1903,  30,  1470,  3528 ;  1904,  37, 1644 ;  Annalen,  1903,  341, 1 ;  1906, 345, 155. 

K.S 


148    THE  NATURE  OF  ORGANIC  REACTIONS 

because,  as  Baeyer  and  Villiger1  have  pointed  out  in  the  case  of 
dianisalacetone,  the  methoxyl  group  in  the  para  position  in  A  would 
be  eliminated  with  the  chlorine  and  yield  a  quinone,  a  reaction 
which  does  not  take  place.  They  also  reject  the  theory  of  Baeyer 
and  Villiger  that  the  colour  is  due  to  the  union  of  the  acid  with 
the  ketone  oxygen,  because  it  has  been  found  in  compounds  of  this 
class  that  the  CO  group  is  less  reactive  than  the  neighbouring  C=C 
group,  and  such  a  union  would  not  explain  the  addition  of  two 
molecules  of  halogen  acid  to  dibenzalacetone,  &c.  Moreover,  an 
unsaturated  compound  containing  no  CO  group,  such  as  anethole, 
isosafrole,  &c.,  forms  yellow  and  red  additive  compounds  with 
hydrogen  bromide  and  picric  acid,  and  the  same  occurs  with 
anthracene  and  phenanthrene.  For  this  and  other  reasons  Vor- 
lander  also  rejects  Thiele's  rule  of  the  existence  of  a  1.4  and  1 .  2 
additive  compound.  Nor  is  the  colour  necessarily  due  to  the  for- 
mation of  a  coloured  ion,  for  then  trimethylammoniumazobenzene 
chloride,  C6H5N  :  N  .  C6H4 .  N(CH3)3C1,  should  be  violet,  like  amino- 
azobenzene  hydrochloride,  CGH5N  :  N .  CGH4NH3C1,  whereas  it  is 
orange,  like  aminoazobenzene.  The  colour  must  therefore  be  due  to 
a  change  in  the  saturation  capacity  of  one  or  more  elements. 

Vorlander  considers  the  interaction  of  two  substances  to  depend 
upon  a  difference  of  potential,  which  falls  slightly  in  the  formation  of 
the  A  coloured  compounds,  but  much  more  in  that  of  the  B  colourless 
compounds.  The  first  stage  in  the  process  of  combination  corre- 
sponding to  the  A  compound  is  compared  to  two  oppositely  charged 
conductors  separated  by  a  dielectric,  in  which  the  charges  are  con- 
centrated at  opposite  points  of  the  conductor ;  the  second,  corre- 
sponding to  the  B  compound,  to  their  discharge  on  coming  into 
contact.  A  strain  is  first  set  up,  followed  by  a  fall  of  energy  in 
the  system.  The  two  phases,  A  and  J5,  are  termed  'addition 
isomerism '. 

They  are  represented  in  the  following  way :  in  the  first  or  colour- 
forming  phase  there  is  no  separation  of  the  constituents  of  HX,  but 
the  attachment  is  that  of  a  molecular  compound ;  in  the  second, 
dissociation  of  HX  occurs  and  the  two  constituents  combine 
additively,  with  loss  of  energy,  forming  the  stable  and  colourless 
compound, 

(HX) 
RCH— CH .  CO .  R     Coloured 

X        H 
RCH— CH .  CO .  R    Colourless 

Ber.,  1902,  35,  1191. 


SUBSTITUTION   IN   THE  AROMATIC  SERIES       149 

If  the  assumption  of  the  existence  of  molecular  ions  is  correct,  the 
first  reaction  will  be  influenced  by  the  nature  of  the  solvent  as  well 
as  by  temperature,  pressure,  and  the  action  of  light,  whereas  in  the 
second,  the  solvent  will  have  little  effect. 


THE  AROMATIC  HYDROCARBONS 

The  aromatic  hydrocarbons,  standing  as  it  were  midway  between 
saturated  and  unsaturated  compounds,  may  be  briefly  considered  here. 

Substitution  in  the  Aromatic  Series.  It  is  well  known  that 
substitution  in  the  nucleus  of  a  monosubstituted  benzene  derivative 
gives  rise  to  one  or  more  isomers.  It  is  rare  to  find  all  three  present 
in  the  product ;  but  usually  the  new  substituent  enters  either  the 
ortho  or  para  position,  or  both  ortho  and  para  positions,  or  on  the 
other  hand  only  the  meta  position.  The  group  already  present 
appeal's  to  possess  a  directing  influence,  which  has  been  embodied  in 
certain  rules  of  substitution.  Hubner l  expresses  it  as  follows :  *  In 
the  replacement  of  hydrogen  in  the  benzene  nucleus  the  entrant 
negative  (acid)  substituent  enters  the  para  position  and  at  the  same 
time  the  ortho  position  to  the  least  negative  or  acid  substituent  already 
present.  It  follows  from  this  that  if  an  acid  (negative)  substituent 
is  already  present  and  a  second  acid  substituent  enters,  the  latter  will 
avoid  the  ortho  and  para  positions  as  far  as  possible  and  enter  mainly 
the  meta  position.' 

Noelting 2  has  expressed  the  same  thing  more  definitely :  '  If 
a  neutral,  basic,  or  weakly  acid  group,  such  as  CH3,  Cl,  Br,  I,  NH2, 
OH,  occupies  position  1,  by  the  action  of  Cl,  Br,  I,  HNO3,  and  H2S04 
the  main  product  will  be  a  para  compound  together  with  varying  but 
always  smaller  quantities  of  ortho  derivatives.  But  if  the  position  1 
is  occupied  by  an  acid  group,  N02,  C02H,  S03H,  the  action  of  the 
above  reagents  produces  mainly  a  meta  compound  together  with 
small  quantities  of  the  ortho  and  para  series.'  Crum-Brown  and 
Gibson3  have  presented  the  rule  in  a  rather  different  form. 
Supposing  the  radical  already  present  forms  a  compound  with 
hydrogen,  which  can  be  converted  by  direct  oxidation  into  the 
corresponding  hydroxyl  compound,  the  new  substituent  will  enter 
the  meta  position,  otherwise  it  will  occupy  the  ortho-para  position. 
Thus  HC1  cannot  be  oxidised  directly  to  HC1O,  but  acetaldehyde 
CH3CHO  gives  CH3COOH.  The  directing  influence  of  chlorine  in 

1  Ber.,  1875,  8,  873.  *  Ber.,  1876,  9,  1797. 

5  Trans.  Chem.  Soc.,  1892,  61,  367. 


150  THE  AROMATIC  HYDROCARBONS 

the  first  case  is  therefore  to  the  ortho-para,  that  of  acetyl  to  the  meta 
position.     The  results  are  given  in  the  form  of  a  table : 


C6H5C1 

Cl 

HC1 

HOC1 

o-p 

C6H5Br 

Br 

HBr 

HOBr 

o-p 

C,H6CH8 

CHS 

HCH3 

HOCH, 

o-p 

C6H5NH3 

NHa 

HNH2 

HONHj 

o-p 

C0H5OH 

OH 

HOH 

HOOH 

o-p 

C6H5NOa 

N02 

HN03 

HON02 

m 

C6H5CCJ2 

CC13 

HCC13 

HOCC13 

o-p 

C6H5COH 

COH 

HCOH 

HOCOH 

m 

C6H5COOH 

COOII 

HCOOH 

HOCOOH 

M 

C6H5S03H 

S03H 

HS03H 

HOS03H 

wt 

CfiH5.CO.CH3 

CO  .  CH3 

HCOCH3 

HOCOCH3 

M 

CCH5CH2.COOH 

CHa  .  COOII 

HCH2  .  COOH 

HOCH2.  COOII 

o-p 

The  authors  point  out  expressly  that  the  rule  is  no  ;  law ',  as  the 
nature  of  the  substituent  has  no  obvious  connection  with  the 
mechanism  of  the  reaction. 

Another  way  of  formulating  the  rule  is  given  by  Armstrong,1  who 
points  out  that  ortho-para  substitution  takes  place  if  an  element 
is  present  in  a  group  in  which  the  atom  attached  to  the  nucleus  is 
only  linked  to  univalent  atoms.  Meta  substitution,  on  the  other 
hand,  occurs  if  the  attached  atom  is  linked  to  multivalent  atoms. 

Vorlander  has  advanced  a  similar  rule  to  the  effect  that  in 
brominating,  sulphonating,  and  nitrating  a  benzene  substitution 
product  CCH5E,  the  substituents  E  have  a  different  influence  accord- 
ing to  whether  the  element  in  the  side-chain  is  saturated  or  not. 
Chloro-  and  broino-benzene,  phenol,  toluene,  benzyl  chloride,  and 
phenylacetic  acid  give  almost  exclusively  para  and  ortho  substitution 
products,  whereas  from  nitrobenzene,  benzenesulphonic  acid,  benz- 
aldehyde,  benzonitrile,  acetophenone,  &c.,  mainly  meta  derivatives  are 
formed.  The  groups  which  give  rise  to  the  entrance  of  nitro  groups 
into  the  meta  position  are  unsaturated  : 

-N02,  —  ON,     -CHO,  —COOH,  — SO.H. 
Those  which  favour  the  ortho-para  position  are  saturated  : 

-Cl,  — Br,  —OH,  — CH3,  — CH2C1,  — CH2.  COOII. 
But  none  of  these  rules  rigidly  express  the  facts.  It  is  difficult  to 
draw  a  definite  line  between  weakly  and  strongly  negative  atoms 
and  groups  as  formulated  by  Hiibner  and  Noelting.  The  Crum- 
Brown-Gibson  rule  does  not  explain  the  formation  of  m-nitraniline 
(NHj  cannot  be  directly  oxidised  to  NH2OH)  nor  the  production  of 
ortho-para  derivatives  from  toluene  (CH4  is  directly  oxi disable  to 
methyl  alcohol  as  Bone2  has  shown).  Vorliinder's  rule  falls  short  in 

1  Trans.  Chem.  SocM  1887.  51,  258.  a  Trans.  Ckem.  Soc.t  1908,  93,  1975. 


SUBSTITUTION  IN  THE  AKOMATIC  SERIES       151 

the  case  of  unsaturated  compounds  such  as  cinnamic  acid,  w-nitro- 
styrene,  and  azobenzene,  which  come  within  the  ortho-para  series. 
Moreover,  there  are  cases  where  all  three  derivatives  are  formed ;  for 
example,  when  nitric  acid  acts  on  toluene.  In  addition  to  ortho  and 
para,  small  quantities  of  meta-nitrotoluene  are  formed.  The  same 
occurs  with  the  action  of  nitric  acid  on  benzoic  acid,  in  which  the 
principal  product  is  the  meta  compound  ;  but  ortho  and  para  nitro- 
benzoic  acids  are  also  produced.  Aniline,  acetanilide,  and  benzanilide 
yield  all  three  nitro  derivatives  and  so  does  acetophenone.  Another 
point  to  remember  is  that  in  cases  where  the  three  isomers  have  not 
been  detected,  one  or  other  may  have  been  overlooked  owing  to  the 
experimental  difficulties  which  attend  the  separation  of  a  small 
quantity.  But  there  are  other  exceptions  in  which  the  formation  of 
the  particular  isomer  and  the  relative  quantity  of  it  are  determined  by 
the  conditions  of  the  reaction.  Acetanilide  and  fuming  nitric  acid 
give  a  mixture  of  ortho  and  para  derivatives ;  in  presence  of  strong 
sulphuric  acid  about  95  per  cent,  of  para  is  produced  ;  but  if  nitrated 
with  nitrogen  pentoxide  in  presence  of  acetic  anhydride  the  product 
is  almost  exclusively  the  ortho  compound.  This  is  in  agreement  with 
the  rule ;  but,  on  the  other  hand,  if  aniline  is  nitrated  in  presence  of 
a  large  quantity  of  strong  sulphuric  acid,  the  main  product  is  meta. 
Similar  observations  have  been  made  with  dimethylaniline,  in  which 
the  presence  of  strong  sulphuric  acid  gives  rise  to  the  meta  derivative 
as  principal  product.  A  very  curious  result  is  obtained  on  intro- 
ducing alkyl  groups  into  toluene  by  the  Fried  el-Crafts  reaction. 
Methyl  enters  mainly  into  the  ortho  position,  propyl  into  the  meta, 
butyl  into  the  meta  and  para,  and  amyl  probably  into  the  para 
position.  Holleman1  does  not  regard  this  fact  as  opposed  to  the 
usual  rule  owing  to  the  complicated  nature  of  the  reaction  and  the 
number  of  products  formed.  Blanksma2  explains  other  exceptions  by 
indirect  substitution,  in  which. the  substituent  first  enters  the  side- 
chain  and  then  passes  into  the  nucleus.  This  applies  to  ortho-para 
substitution  in  the  nitration  of  aniline.  Direct  or  meta  substitution 
is  assumed  to  occur  when  sulphuric  acid  is  present.  This  view 
cannot  be  generally  applicable  seeing  that  on  nitrating  or 
brominating  bromobenzene  indirect  substitution  cannot  occur ;  never- 
theless the  products  are  ortho  and  para  compounds. 

Although  the  general  rules  cited  above  in  different  forms  are 
observed  in  the  larger  number  of  cases,  it  does  not  follow  that  the 

1  Lie  direkteEinfuhmng  ton  Substituenten  in  den  Benzolkern,  p.  196,  A.  F.  Holleman. 
Veit,  Leipzig,  1910. 

8  Rec.  des  trav,  chim.  Pays- Bos,  1902,  21,  281 ;  1904,  23,  202. 


152  THE  AROMATIC  HYDROCARBONS 

proportion  of  ortho  and  para  is  retained  under  different  conditions 
or  on  introducing  different  substituents.  For  example,  in  sul- 
phonating  phenol,  the  higher  the  temperature,  the  more  para  relatively 
to  ortho  compound  is  formed  ;  in  brominating  toluene  the  para  com- 
pound is  the  main  product  (60  per  cent.),  but  in  nitration  it  is  the 
ortho  compound  which  predominates  (56  per  cent.).  Bromination 
of  benzoic  acid  yields  only  the  meta  compound,  but  nitration  yields 
all  three  nitro  compounds.  The  character  and  amount  of  by-products 
are  subject  to  considerable  variation.  If  para  is  the  main  product, 
some  ortho  is  usually  formed,  but  little  or  no  meta  compound.  If 
ortho  is  the  main  product,  para  is  found  with  a  little  meta.  If, 
finally,  meta  is  the  chief  product,  either  ortho  or  para  accompanies 
it,  together  with  small  quantities  of  the  third  isomer.  None  of  these 
observations  are  without  exceptions.  Benzenesulphonic  acid  gives 
mainly  the  m-disulphonic  acid  (68  per  cent.)  and  the  rest  is  para  free 
from  ortho.  Benzoic  acid  gives  mainly  w-sulphobenzoic  acid,  and 
again  the  para  is  the  only  by-product. 

In  regard  to  the  rules  which  determine  the  entrance  of  substituents 
into  higher  substituted  derivatives  of  benzene,  it  appears  in  the  case 
of  the  halogens  that  when  the  first  two  hydrogen  atoms  have  been 
replaced  in  the  ortho,  meta,  or  para  positions,  further  substitution 
mainly  follows  in  a  direction  which  leads  to  a  1.2.4.5  derivative 
whatever  the  nature  of  the  entrant  group  \ 


Theories  of  Benzene  Substitution.  Holleman  in  his  treatise  on 
'Die  Einfuhrung  von  Substituenten.  in  den  Benzolkern '  has  dis- 
cussed very  fully  the  various  theories  which  have  been  advanced  at 
different  times  to  explain  the  rules  of  substitution.  Armstrong2 
adopts  the  view  that  addition  precedes  substitution ;  that  in  ortho- 
para  substitution,  the  additive  compound  results  from  the  union  of 
the  reacting  molecule  with  the  carbon  atom  to  which  the  first  radical 
is  attached,  whilst  in  meta  substitution  the  additive  compound  is 
formed  by  the  union  of  the  reacting  molecule  with  the  radical,  which 
usually  contains  an  unsaturated  group.  In  view  of  Bamberger's  and 

1  Cohen  and  Dakin,  Trans.  Chem.  Soc.,  1904,  85,  1274  :  Cohen  and  Hartley. 
{bid.,  1905,  87,  I860. 

•  Trans.  Chem.  Soc.,  1887,  51,  258. 


THEORIES  OF  BENZENE  SUBSTITUTION  153 

Chattaway's  observations  on  isomerie  change  where  a  group  passes 
from  side-chain  to  nucleus,  yielding  in  the  majority  of  cases  ortho 
and  para  derivatives  (Part  II,  p.  371),  this  view  cannot  be  sustained. 

Fliirscheim's  Theory.1  Fliirscheim  bases  his  view  of  substitution 
on  Werner's  theory  of  maximum  disposable  affinity  which  may  be 
variously  distributed  according  to  the  nature  of  the  attached  atoms 
as  previously  explained  (p.  87).  Elements  which  have  a  stronger 
affinity  for  carbon  than  hydrogen,  such  as  chlorine,  tervalent  nitrogen 
in  the  amino  group,  oxygen  in  hydroxyl,  &c.,  attach  themselves 
more  firmly  than  saturated  atoms,  such  as  nitrogen  in  the  nitro 
group  and  in  quinquevalent  salts  of  amino  compounds,  carbon  in 
carboxyl,  and  sulphur  in  the  sulphonic  acid  group,  &c.  The  former, 
by  absorbing  more  of  the  affinity  of  nuclear  carbon,  lessen  the 
amount  which  link  the  ortho  carbon  atoms,  leaving  a  larger  quantity 
available  in  the  ortho  and  para  positions,  for  the  attachment  of  new 
substituents,  whilst  the  latter,  which  are  less  firmly  attached,  will 
leave  more  available  for  attachment  in  the  meta  position.  If  the 
strength  of  affinity  be  denoted  by  thick  and  thin  lines  the  distribu- 
tion in  the  case  of  chlorine  and  the  sulphonic  group  will  appear  as 
follows : 


Such  apparent  anomalies  as  the  entrance  of  the  nitro  group  into 
the  para  position  in  phenylacetic  acid  and  into  the  meta  position  in 
phenylglycine  is  explained  in  the  same  way  by  a  different  distribu- 
tion of  affinity. 

<^ 
H 
Phenylacetic  acid. 

C6H5-CH-C/ 

I  X)H 

NH2 

Phenylglycine. 
1  J.  prakt.  Chcrn.,  1902,  66,  321  ;  1905,  71,  497. 


154  THE  AEOMATIC  HYDKOCAKBONS 

But  this  explanation  is  scarcely  satisfactory,  for,  as  Obermiller 
points  out,  methyl,  which  is  a  saturated  group  and  therefore  weakly 
attached,  produces  ortho-para  substitution  in  place  of  meta. 

Without  discussing  in  detail  the  other  weak  points  in  the  theory, 
attention  may  at  least  be  directed  to  one,  namely  the  difficulty  of 
explaining  why  ortho  substitution  in  the  first  case  should  occur  to 
the  exclusion  of  meta,  and  why  in  the  second  case  meta  substitution 
should  be  produced  to  the  exclusion  of  ortho,  seeing  that  in  both,  the 
ortho  and  meta  carbon  atoms  are  joined  by  a  weak  and  strong 
affinity,  and  have  consequently  a  precisely  equal  affinity  value. 
Moreover,  as  Holleman  observes,  the  idea  of  a  strong  and  weak 
attachment  is  purely  relative ;  there  is  no  definite  line  of  demarca- 
tion, nor  has  any  group  a  fixed  and  unalterable  affinity  value  in 
relation  to  the  nucleus.  The  nitro  group  in  nitrobenzene  is  extremely 
stable  compared  with  the  fourth  nitro  group  in  tetranitrophenol,  which 
water  will  remove  in  the  form  of  nitrous  acid. 

Tschitschibabin's  theory  of  substitution l  bears  a  close  resemblance 
to  that  of  Fliirscheim.  It  is  based  upon  the  principle  already 
explained  (p.  87)  that  unsaturated  atoms  mutually  saturate  one 
another  up  to  a  certain  point,  and  that  in  consequence  the  carbon 
atoms  in  benzene  are  more  saturated  than  the  four  in  dihydrobenzene 
or  the  two  in  tetrahydrobenzene.  Unsaturated  groups,  such  as  NH2, 
by  appropriating  some  of  the  affinity  of  the  carbon  atom  of  the  ring 
leave  less  at  the  disposal  of  the  latter,  and  consequently  the  ortho 
and  also  the  para  carbon  atoms  are  less  saturated.  Nitrogen  in  the 
nitro  group  is,  however,  more  saturated  than  in  the  ammo  group,  and 
consequently  the  attached  carbon  atom  is  less  saturated  and  has  more 
affinity  at  the  disposal  of  the  ortho  carbon  atoms,  which  leaves  less 
for  the  meta  carbon  atoms.  The  meta  carbon  atom  is  thereby  less 
saturated.  Aldehyde  and  carboxyl  groups  behave  in  the  same  way 
as  the  nitro  group  and  for  the  same  reasons.  According  to  this  view 
methyl  should  have  a  meta  orienting  effect,  which  is  exactly  the 
reverse  of  the  fact.  Tschitschibabin  supposes  that  unsaturation  is 
manifested  by  addition  to  the  unsaturated  atoms,  and  that  it  may 
occur  either  with  nuclear  carbon  or  hydrogen  or  with  the  atoms  of 
a  side-chain  according  to  the  character  of  the  unsaturated  atom  or 
group  and  the  nature  of  the  addendum.  He  represents  the  process 
by  the  following  schemes,  in  which  X  represents  the  substituent  and 
YZ  the  addendum. 


1  J.  prakt.  Chtm.,  1912,  86,  397. 


HITSCHIBABIN'S  THEORY  155 


X 

/\ 

/HY    -> 


it 


In  this  way  the  ortho-para  and  the  meta  laws  of  substitution  are 
explained,  but  the  method  of  addition  scarcely  accords  with  modern 
views.  The  main  difference  between  this  and  the  former  theory 
seems  to  be  that  whereas  Fltirscheim  regards  each  group  as  appro- 
priating a  definite  amount  of  chemical  affinity  under  all  circum- 
stances, unsaturation,  according  to  Tschitschibabin,  is  a  variable 
quantity  depending  on  environment. 

It  appears  to  us  that  the  author  confuses  the  notion  of  affinity  as 
manifested  by  saturated  and  unsaturated  atoms.  Unsaturated  atoms 
are,  like  oppositely  charged  conductors,  at  a  higher  potential  than 
saturated  atoms.  Saturated  atoms  have  a  lower  energy  content  and 
therefore  exhibit  a  firmer  union.  This  firmer  union  will  affect  both 
atoms  alike,  and  the  second  will  lose  as  much  free  affinity  as  the 
first  and  will  therefore  not  gain  by  the  transaction  as  Tschitschibabin 
seems  to  assume. 

To  explain  the  laws  of  substitution  Obermiller l  adopts  the  Glaus 
diagonal  formula  for  benzene,  where  each  carbon  atom  of  the 
nucleus  is  simultaneously  linked  to  an  ortho  and  para  carbon  atom 
which  are  thus  similarly  connected.  He  also  regards  substitution  as 
a  direct  process  not  preceded  by  addition. 

Substituents  are  divided  into  two  classes :  those  which  promote 
substitution  and  those  which  hinder  it.  The  orienting  effect  of  the 
first  is  directed  towards  the  ortho  and  para  positions,  that  of  the 
second  towards  the  meta  position. 

The  division  is  not  very  clearly  marked,  and  depends  on  the  ease 
or  difficulty  with  which  the  second  and  third  member  of  the  sub- 
stituting group  can  be  introduced  into  the  nucleus.  The  meta- 

1  Die  orientiercnden  Einjliisse  und  der  Bensrtkern,  by  J.  Obermiller.  J.  A.  Earth, 
Leipzig,  1909. 


156  THE  AROMATIC   HYDROCARBONS 

orienting  influence  of  such  groups  as  N02,  S03H,  and  C02H  is  put 
down  to  steric  hindrance  due  to  the  space  occupied  by  the  group. 
This  effect  may  under  certain  circumstances  be  suppressed  if  the 
orienting  influence  of  an  ortho-para  substituting  group  is  present,  as, 
for  example,  in  the  nitration  of  w-chloronitrobenzene  when  the 
second  nitro  group  under  the  orienting  influence  of  the  chlorine 
atom  enters  the  ortho  position  to  the  first  group.  Then,  it  may  be 
asked,  why  does  the  nitro  group  frequently  enter  the  ortho  position 
rather  than  the  para,  where  steric  hindrance  would  have  less  effect  ? 

Oberniiller  attempts  to  show  that  a  low  temperature  and  a  slower 
rate  of  reaction  overcome  steric  hindrance,  and  he  cites  the  case  of 
sulphonating  phenol  in  the  cold  and  in  dilute  solution,  which  yields 
the  ortho-sulphonic  acid  mainly,  whereas  higher  concentration  and 
higher  temperature  give  the  para  compound. 

In  other  respects  Obermiller  adopts  Werner's  theory  of  valency, 
and  his  views,  though  somewhat  differently  expressed,  bear  a  certain 
resemblance  to  those  of  Flurscheim.  A  weak  affinity  between  the 
first  substituent  and  nuclear  carbon  will  strengthen  that  between  the 
carbon  atoms  in  the  ortho  and  para  position  and  weaken  the  affinity 
of  the  latter  for  hydrogen,  which  is  more  easily  replaced  in  con- 
sequence. The  closer  the  union  between  atoms,  the  greater  will  be 
their  mutual  influence,  so  that  the  ortho  carbon  atoms  will  be  more 
affected  by  substitution  than  those  in  the  para  position ;  but  steric 
hindrance  may  supervene  and  reverse  the  result.  If  steric  hindrance 
prevents  substitution  in  the  para  position  as  well,  then  meta  substi- 
tution will  occur. 

The  author,  in  short,  lays  down  so  many  rules  and  assumes  so 
many  modifying  circumstances  that  it  is  not  surprising  to  find  that 
the  examples  given  fit  in  satisfactorily  with  one  or  other  of  the 
possible  explanations. 

Holleman  has  suggested  a  less  speculative  and  more  reasonable 
explanation.  Assuming  Kekule's  formula  for  benzene,  he  supposes 
a  radical  X,  being  already  present  in  the  benzene  nucleus,  may 
promote  or  retard  addition  of  the  new  substituent  to  the  adjoining 
double  bond.  If  it  promotes  addition,  an  ortho  compound  will 
result.  Conjugation  may  cause  addition  in  the  para  position,  accord- 
ing to  Thiele's  theory  (p.  133),  in  the  same  fashion.  On  the  other 
hand,  the  addition  in  position  2 .  3  is  uninfluenced  by  X,  as  it  does  not 
adjoin  the  double  bond.  In  other  words,  addition  is  influenced  by 
X  in  positions  1 .  2  and  1 . 6,  but  not  in  2.3.  The  idea  may  be 
illustrated  in  the  following  manner.  Let  us  suppose  CCH5X  to  be 
nitrated  ;  three  additive  compounds  may  be  formed. 


HOLLEMAN'S  THEORY 


157 


Ortho. 


Mota. 


By  subsequent  removal  of  water  a  para,  ortho,  or  meta  nitro-compound 
is  produced.  If  X  accelerates  the  reaction,  substitution  follows  the 
para-ortho  rule,  which  may  lead  to  the  exclusion  of  any  meta  com- 
pound. If  X  has  no  such  accelerating  action,  smaller  or  larger 
quantities  of  meta  compound  will  be  formed.  Examples  are  afforded 
by  the  nitration  of  phenol  and  toluene.  In  the  first  case,  where  the 
rate  of  the  reaction  is  high,  ortho  and  para  nitro-compounds  only  are 
formed  ;  in  the  second,  where  the  rate  is  slower,  a  certain  amount  of 
meta  compound  is  produced.  If  X  has  a  retarding  effect,  addition  at 
2 .  3  predominates.  This  view  fits  in  very  neatly  with  the  observa- 
tion that  meta  compounds  are  often  accompanied  by  smaller  quanti- 
ties of  ortho,  for  here  the  first  addition  occurs  at  2 . 3  and  then  at 
2.  1,  in  which  position  2  is  common  to  both. 

Collie,1  by  means  of  a  model  in  which  the  carbon  atoms  with  the 
attached  hydrogen  revolve,  has  illustrated  the  movement  of  the 
carbon  atoms  of  benzene,  whereby  it  is  made  to  pass  through  various 
phases.  These  phases  may  be  represented  in  a  plane  by  means  of 
figures  in  which  the  Kekule  and  centric  formulae  recurrently  appear, 
as  representing  certain  states  of  the  nucleus. 


Centric 
formula. 


Kekule 
formula. 


Last 
phase. 


Supposing  addition  to  the  original  unsaturated  substituent  to 
precede  substitution,  the  orientation  of  the  newly  attached  group  will 
be  dependent  on  the  phase  in  which  the  addition  occurs.  If  nitro- 
benzene were  chlorinated,  an  additive  compound  C6H5N02 .  C12  will 
first  be  formed.  In  the  first  phase  we  may  suppose  the  N02  group 
to  occupy  the  position  of  one  of  the  external  hydrogen  atoms,  and,  in 


1  Trans.  Client.  Soc.,  1897,  71,  1013. 


158 


THE  AROMATIC  HYDROCARBONS 


the  last,  that  of  one  of  the  internal  hydrogen  atoms.  In  the  latter 
position  chlorine  would  be  brought  into  close  contact  with  the 
hydrogen  atoms  and  substitution  would  take  place  in  the  meta 
position. 

N0tci, 


But,  on  the  other  hand,  when  nitric  acid  is  allowed  to  react  with 
chlorobenzene,  no  such  additive  compound  would  be  formed,  and  the 
attraction  of  the  three  hydrogen  atoms  attached  to  the  2.4.6  carbon 
atoms  might  be  just  sufficient  to  determine  its  reaction  with  them 
and  so  produce  ortho  and  para  compounds. 


It  must  be  confessed  that  the  second  explanation  is  not  quite  so 
convincing  as  the  first. 

Lapworth 1  bases  his  views  on  the  dyad  and  triad  type  of  isomeric 
change  (Part  II,  p.  318)  in  which  migration  occurs  from  an  a  to  a  ft 
atom  with  change  of  valency  and  from  an  «  to  a  y  atom  with  change 
of  linkage. 

A=B      ±      A— B 


«   ft  y 
A:B.C 


«    P    7 
A.B:C 


The  idea  has  been  extended  by  introducing  a  double  migration, 
taking  place  successively  in  opposite  directions,  thus : 

A.B:C      ±    A:B.C      ±    A.B:C 


1  Trans.  Chem.  Soc.,  1898,  73,  445;  1901,  79,  1265. 


LAPWORTH'S   THEORY  159 

which  may  recur  through  a  series  of  alternate  singly  and  doubly 
linked  atoms  such  as  exist  in  benzene  (Kekule's  formula). 

The  process  is  illustrated  by  isomeric  change  from  side-chain  to 
nucleus,  as  for  example  in  the  case  of  benzenesulphamic  acid,  when 
a  sulphonic  acid  group  wanders  from  nitrogen  to  the  nucleus  to  form 
ortho  and  para  anilinesulphonic  acids  (Part  H,  p.  371). 

NH,  NH, 

[     and 


The  sulphonic  group  wanders  to  the  first  y  atom  in  the  ortho 
position  and  to  the  next  y  carbon  in  the  para  position,  whilst  the 
hydrogen  it  displaces,  wanders  in  the  opposite  direction. 

The  meta  change  is  effected  in  the  same  way  by  migration  in  two 
directions  ;  but  owing  to  the  unsaturation  of  the  side-chain,  the 
wandering  group  is  farther  removed  from  the  nucleus.  This  may  be 
illustrated  in  the  case  of  the  sulphonation  of  nitrobenzene. 

«0 

HOOH 


In  this  case  the  hydrogen  migrates  from  the  first  y  position  to  the 
next  y  position  and  thence  to  the  oxygen  of  the  nitro  group,  and  the 
sulphonic  groups  make  the  reverse  journey. 

The  conditions  underlying  the  meta  rule  are  formulated  by 
Lapworth  as  follows :  t  Where  a  substitution  product  is  formed  by 
isomeric  change  of  a  product  of  addition  or  substitution  in  the  side- 
chain  in  which  the  substituting  radical  is  separated  from  the  benzene 
nucleus  by  two  intermediate  atoms,  a  meta  substitution  derivative  must 
be  produced  or  replacement  of  the  side  group  by  the  new  substituting 
radical  will  occur.' 

Direct  substitution  in  the  nucleus  is,  according  to  Lapworth,  deter- 
mined by  addition  followed  by  cleavage  as  formulated  by  Armstrong 
and  Holleman. 


160  THE  AROMATIC  HYDROCARBONS 

Electronic  Theory  of  Substitution.  H.  S.  Fry l  has  elaborated 
an  interesting  theory  of  substitution,  which  is  based  on  the  assump- 
tion that  the  atoms  can  either  give  or  absorb  electrons,  or,  in  other 
words,  can  function  both  with  positive  and  negative  valencies,  and 
that  it  is  this  opposition  of  electronic  characters  which  bind  the 
atoms  in  a  molecule.  Benzene  is,  therefore,  represented  by  a  ring 
of  carbon  atoms,  linked  alternately  by  positive  and  negative  valencies 
to  the  positive  and  negative  valencies  of  hydrogen. 


This  being  assumed,  it  follows  that  in  the  formation  of  di-deriva- 
tives  the  dominant  valency  in  the  ortho  and  para  position  to  the  sub- 
stituent  group  will  be  of  the  same  sign,  that  in  the  meta  position  of 
opposite  sign.  Thus,  a  positive  group  will  attach  itself  to  a  C  - 
atom  and  a  negative  group  to  a  C  +  atom.  Similar  atoms  and 
groups  should  therefore  substitute  in  the  meta  position  and  groups 
of  different  sign  in  the  ortho  and  para  positions.  But  in  chlorina- 
tion,  the  chlorine  atoms  form  ortho  and  para  di-derivatives.  How 
is  this  explained  ?  Every  atom  or  group  may  react  by  virtue  of  its 
+  or  -  valencies  and  may  be  +  in  one  compound  and  -  in  another, 
or,  indeed,  both  +  and  -  in  the  same  molecule,  such,  for  instance, 
as  the  atoms  in  the  chlorine  molecule,  or  the  two  carboxyl  groups  in 
phthalic  and  terephthalic  acids. 

The  theory,  moreover,  demands  the  existence  of  two  mono-deriva- 
tives in  which  the  substituent  is  attached  to  an  electropositive  or  an 
electronegative  carbon  atom  by  an  electropositive  or  negative  valency. 


C6H5X  and  CgH^X 
The  difficulty  is  overcome  by  assuming  a  form  of  tautomerism, 

1  J.  Amer.  Chem.  Soc.,  1912,  34,  664;  1914,  36,  248,  262,  1035:  1915,  37,  855. 
2368  ;  1916,  38,  1323. 


ELECTRONIC  THEOKY  OF  SUBSTITUTION          161 

termed  by  the  author  electronic,  in  which  isomeric  equilibrium  be- 
tween the  two  forms  is  supposed  to  exist. 

The  same  kind  of  electronic  tautomerism  may  occur  in  other 
compounds,  such  as  nitric  acid. 

-        +  +        - 

HO.  NO,    ^±    HO.  NO, 

The  theory,  in  short,  is  so  mobile,  so  adaptable  and  so  ingeniously 
applied  as  to  explain  most  of  the  facts  of  substitution  as  well  as 
many  reactions  of  aromatic  compounds ;  but  cannot  be  discussed  in 
greater  detail,1 

1  The  theory  has,  however,  not  escaped  criticism :  see  Holleman,  J.  Amer. 
Chem.  Soc.,  1914,  26,  2495. 


PT.  I 


162 


CATALYTIC  KEACTIONS  OF  OKGANIC  COMPOUNDS 

Catalytic  Reduction.  Platinum  and  palladium  in  conjunction 
with  hydrogen  have  been  frequently  used  as  reducing  agents,  and  it 
has  long  been  known  that  unsaturated  hydrocarbons  could  be  con- 
verted into  paraffins  and  the  oxides  of  nitrogen  into  ammonia  by 
passing  a  mixture  of  the  vapour  or  gas  and  hydrogen  over  the  heated 
metal.  The  process  is  a  typical  catalytic  or  contact  reaction,  inasmuch 
as  the  metals  greatly  accelerate  reduction  without  undergoing  any 
fundamental  change  in  composition  or  quantity,  or  bearing  any  mole- 
cular relation  to  the  amount  of  material  transformed. 

It  is  not  our  intention  to  enter  on  a  discussion  of  the  mechanism 
of  the  process,  about  which  there  is  some  diversity  of  opinion,  but 
merely  to  record  its  application  in  organic  synthesis. 

Bredig1  was  the  first  to  obtain  colloidal  platinum  by  passing 
a  current  between  electrodes  of  the  metal  below  the  surface  of  water. 
The  metal  appears  to  pass  into  solution,  but  the  latter  has  none  of 
the  physical  characters  of  a  true  solution,  for  it  neither  diffuses 
through  animal  membranes  nor  exhibits  osmotic  pressure.  It  is 
a  pseudo  or  colloidal  solution.  He  noticed  its  reducing  action  on 
nitrites  and  its  effect  in  bringing  about  the  union  of  hydrogen  and 
oxygen. 

In  1902 2  Paal  found  that  colloidal  solutions  of  metallic  oxides  and 
metals  could  be  produced  by  adding  alkali  to  the.  metallic  salts  in 
presence  of  the  sodium  salts  of  protalbinic  and  lysalbinic  acid  (hydro- 
lytic  products  of  protein),  which  act  as  '  protecting  agents  '.  Later,3 
he  prepared  colloidal  palladium,  platinum,  and  indium  by  a  similar 
method,  using  first  hydrazine  sulphate  and  afterwards  free  hydrogen 
as  the  reducing  agent.  The  colloidal  solutions  in  water  and  alcohol 
are  very  active,  and  in  presence  of  hydrogen  reduce  such  substances 
as  oleic,  cinnamic,  maleic,  and  funiaric  acids,  to  the  saturated 
condition. 

Wallach 4  has  since  carried  out  numerous  experiments  by  Paal's 
palladium  method  and  finds  that  ethylene  compounds  can  be  reduced, 
no  matter  where  the  ethylene  bond  occurs,  and  that  the  reduction 
can  be  effected  with  or  without  solvent  and  at  the  ordinary  tempera- 
ture, thus  excluding  the  possibility  of  isomeric  change.  The  reaction 

1  Anorganische  Fermente,  by  G.  Bredig.     Leipzig,  1901. 

2  Ber.,  1902,  35,  2195,  2206,  2227. 

8  Ber.,  1905,  38,  1406,  2414;  1907,  40,  2209;  1908,41,  805,  2273;  1909.  42, 
3930. 

4  Annalen,  1911,  381,  52. 


CATALYTIC  EEDUCTION  163 

can  be  so  regulated  that  the  ketone  group  in  aft  unsaturated  ketones 
is  only  slightly  attacked. 

In  the  meantime  Fokin,  who  had  been  experimenting  on  electro- 
lytic reduction  with  different  metals  as  electrodes,  found  that  those 
metals  which  are  known  to  occlude  hydrogen  have  the  strongest 
reducing  action.  He  subsequently  observed  that  the  solvent  also 
plays  a  part,  and  that  whilst  one  solvent  will  promote,  another  will 
prevent  reduction. 

Later l  he  introduced  platinum  and  palladium  black,  and  showed 
that  oleic  acid  in  ether  solution  in  presence  of  these  metals  is  reduced 
to  stearic  acid  by  passing  in  hydrogen  at  the  ordinary  temperature 
or  in  presence  of  nickel  and  cobalt  at  a  high  temperature.  With 
colloidal  platinum  he  succeeded  in  reducing  a  number  of  unsaturated 
organic  acids  and  also  acrolein,  nitrobenzene,  &c.,  but  not  the 
aromatic  hydrocarbons. 

Willstatter 2  then  took  up  the  subject  and  improved  and  simplified 
the  process  of  reduction  by  using  colloidal  platinum,  prepared 
according  to  Low.3  The  method  consists  in  reducing  platinic 
chloride  with  formaldehyde  in  alkaline  solution.  The  precipitate  is 
then  washed  by  decantation,  until  the  platinum  hydrosol  begins  to 
pass  into  solution,  and  filtered.  The  product,  which  is  carefully 
excluded  from  the  air,  is  very  active,  and  is  capable,  in  presence  of 
hydrogen,  of  effecting  the  complete  reduction,  not  only  of  unsaturated 
compounds,  but  also  of  benzene  and  naphthalene,  which  yield  cyclo- 
hexane  and  deca"hydronaphthalene  respectively,  and  other  aromatic 
hydrocarbons  and  compounds  such  as  phenol  and  benzole  acid,  which 
give  the  hexahydro- derivatives.  The  colloidal  metal  can  be  used 
with  various  solvents.  In  the  examples  named,  glacial  acetic  acid 
was  added  to  the  substance.  The  reducing  activity  is,  however, 
dependent  on  the  absence  of  certain  substances,  especially  sulphur 
compounds,  which  appear  to  arrest  the  action  completely. 

Skita 4  has  introduced  palladious  chloride  in  aqueous  or  alcohol- 
aqueous  solution  in  presence  of  gum  arabic  as  protective  colloid. 
Under  the  action  of  hydrogen  the  palladium  salt  is  reduced  to  the 
colloidal  metallic  condition  and  has  effected  the  reduction  of  a  number 
of  organic  compounds  such  as  unsaturated  ketones  of  the  aliphatic 
and  aromatic  series. 

d-Pulegone  was  reduced  by  hydrogen  at  two  atmospheres  pressure 
in  presence  of  colloidal  platinum  to  d-rnenthone ;  other  reducing 

1  Chetn.  ZentralU. ,  1906,  vol.  ii,  p.  758  ;  1907,  vol.  ii,  p.  1324. 

2  Per.,  1908,  41,  1475  ;  1912,  45,  1471.  3  Ber.,  1890,  23,  289. 
4  Btr.,  1909,  42,  1627  ;  1910,  43,  3393. 

M2 


164  CATALYTIC  REACTIONS  OF  ORGANIC  COMPOUNDS 

agents  yield  the  laevo  compound.  In  mesityl oxide  the  ethylene 
group  is  reduced,  but  the  ketone  group  remains  intact,  and  the 
same  is  true  of  phorone ;  but  by  raising  the  pressure  to  five 
atmospheres  the  latter  is  converted  into  methyl  isobutyl  carbinol. 
Whilst  Sabatier  and  Senderens'  method  (see  below)  leads  to  the  rupture 
of  the  cyclopropane  ring  in  thujene,  Tschugaeif1  found  that  platinum 
black  and  hydrogen  at  the  ordinary  temperature  gave  thujane. 
Rise  of  temperature  also  has  an  effect.  Phenanthrene,  for  example, 
when  reduced  with  palladium  at  the  ordinary  temperature  yields 
tetrahydrophenanthrene,  but  at  160°  the  octahydride  is  formed.  It 
will  be  seen  from  the  foregoing  examples  that  the  action  of  finely 
divided  platinum  and  palladium  affords  an  effective  and  easily 
regulated  reduction  method  of  very  extended  application. 

The  Sabatier-Sendereiis  Method.2  The  method  consists  in 
passing  the  vapour  of  the  substance  to  be  reduced,  mixed  with  pure 
hydrogen,  over  finely  divided  nickel  and  certain  other  metals  at  an 
optimum  temperature.  The  process  originated  in  the  observation 
that  certain  metals  could  be  made  to  combine  with  nitrogen  peroxide. 
An  attempt  to  produce  similar  compounds  with  acetylene  led  the 
authors  to  pass  the  gas  over  finely  divided  metals  (nickel,  cobalt, 
iron,  and  platinum),  with  the  result  that  it  decomposed  with  incan- 
descence. Further  experiments  carried  out  with  ethylene  at  a  tem- 
perature of  300°  yielded  a  similar  result ;  carbon  was  deposited,  but 
the  gas  evolved  proved  to  be  ethane.  Thus  the  saturated  hydro- 
carbon was  probably  formed  at  the  expense  of  the  hydrogen  of  the 
unsaturated  compound.  This  led  the  authors  in  1899  to  study 
the  reducing  action  of  finely  divided  metals,  in  conjunction  with 
hydrogen,  on  a  variety  of  organic  compounds.  Nickel  proved  to 
be  the  most  active,  but  cobalt,  iron,  copper,  and  platinum  were 
also  found  to  effect  reduction,  the  activity  varying  in  different 
cases.  Thus  only  nickel  and  cobalt  can  hydrogenate  the  aromatic 
nucleus. 

Copper  is  less  active  than  nickel,  and  in  certain  cases  where  the 
latter  catalyst  carries  the  reduction  too  far,  metallic  copper  may  be 
substituted.  Very  important  factors  are  temperature  and  pressure, 
for  it  appears  that  these  are  probably  reversible  reactions,3  in 
which  the  balance  may  shift  under  varying  conditions.  This  will 
explain  the  existence  of  an  optimum  temperature  for  each  reaction 
and  the  change  of  product  with  change  of  pressure.  It  is  usual  to 

1  Compt.  rend.,  1910,  151,  1058. 

2  Ber.,  1911,  44,  1984.     See  also,  La  Catalyse  en  Chimb  Organique,  by  P.  Sabatier. 
Be~ranger,  Paris,  1913. 

3  Ipatievv,  Ber.,  1907,  40,  1270. 


METHOD  OF  SABATIER  AND   SENDERENS         165 

explain  the  reducing  action  of  the  metal  by  the  formation  of  an 
unstable  hydride,  a  view  which  accounts  for  the  numerous  cases  of 
dehydrogenation,  when  the  metal  robs  the  compound  of  its  hydrogen. 
But  Ipatiew's  discovery  of  the  almost  equally  efficient  action  of  nickel 
oxide,  especially  in  presence  of  hydrogen  under  pressure,  seems  to 
point  to  the  intermediate  formation  of  water,  which,  according  to 
Ipatiew,  loses  its  hydrogen  in  an  active  form,  regenerating  the 
metallic  oxide.  The  view  receives  some  confirmation  from  Brunei's 
observation1  that  phenol  is  readily  reduced  to  cyclohexanol  by 
vaporising  the  phenol,  previously  liquefied,  by  the  addition  of  water, 
that  is,  in  presence  of  water  vapour.  The  advantage  of  the  Sabatier- 
Senderens  over  the  preceding  methods  is  the  rapidity  of  the  process 
and  the  large  quantities  of  material  which  can  be  treated  in  a  short 
time ;  its  defect  is  the  necessity  of  using  rather  high  temperatures 
(150-200°)  and  the  consequent  difficulty  of  avoiding  secondary 
reactions,  polymerisation,  isomeric  change,  and  occasionally  carboni- 
sation. 

The  operation  is  conducted  as  follows  :  to  obtain  a  large  metallic 
surface,  pieces  of  pumice  are  soaked  in  nickel  nitrate  solution  and 
heated  to  convert  the  nitrate  into  oxide.  The  pumice  is  then  intro- 
duced into  a  hard  glass  tube  about  two  to  three  feet  long  and  placed 
in  a  hot-air  furnace.  The  oxide  is  reduced  at  a  temperature  of  320- 
350°  in  a  current  of  hydrogen,  carefully  purified  and  freed,  more 
especially,  from  traces  of  sulphur  and  halogen,  which  destroy  the 
activity  of  the  catalyst.  The  temperature  is  then  regulated  according 
to  the  nature  of  the  substance  to  be  reduced,  which  is  introduced 
with  the  hydrogen  in  a  steady  stream.  If  gaseous,  the  two  gases  are 
admitted  simultaneously ;  if  liquid,  the  substance  is  dropped  from 
a  tap-funnel  into  the  end  of  the  tube ;  if  solid,  it  is  melted  and 
vaporised  in  a  current  of  hydrogen. 

We  will  now  consider  briefly  the  effect  of  this  method  of  reduction 
on  various  organic  compounds.  Among  the  earliest  experiments 
conducted  by  Sabatier  and  Senderens  was  the  reduction  of  carbon 
monoxide  and  dioxide.  The  former  at  250°  and  the  latter  at  300°  yield 
methane  and  water. 

Olefines  and  Acetylenes.  The  interesting  observation  was  made 
that  when  acetylene  is  reduced  with  excess  of  hydrogen  at  200°, 
liquid  condensation  products  are  formed,  consisting  mainly  of 
paraffins  and  closely  resembling  American  petroleum.  A  second 
treatment  of  the  material  produced  a  certain  quantity  of  hydro- 
aromatic  hydrocarbons  or  napWienes  corresponding  in  character  to 

1  Compt.  rend.,  1904,  137,  1268. 


166    CATALYTIC  REACTIONS  OF  ORGANIC  COMPOUNDS 

the  Caucasian  product,  whilst  if  the  reduction  was  conducted  at 
300°  some  of  the  hydrocarbons  were  converted  into  unsaturated 
cyclic  hydrocarbons  and  the  product  resembled  Galician  petroleum 
in  character. 

The  higher  acetylenes  behave  differently.  Diacetylene  with  copper 
as  catalyst  yields  ethylbenzene  and  other  substances  in  smaller 
quantity  ;  nickel,  on  the  other  hand,  yields  ethylcyclohexane.  The 
difference  between  the  two  catalysts  is  also  brought  out  in  the  case 
of  heptine  C7H12,  copper  giving  heptene  C7HU  and  polymerisation 
products  (di-  and  tri-heptene),  and  nickel  effecting  complete  reduction 
to  heptane.  This  difference  in  action  of  the  catalysts  is  explained 
by  Sabatier  on  the  assumption  that  the  metal,  under  varying  con- 
ditions of  temperature,  is  capable  of  forming  different  hydrides,  and 
thus  producing  lower  and  higher  states  of  hydrogenation. 

Aromatic  Hydrocarbons.  Aromatic  hydrocarbons  (benzene  and 
homologues)  are  readily  converted  into  hexahydro-derivatives  at 
180°,  and  compounds  with  unsaturated  side-chains  yield  the  corre- 
sponding cycloparaffins.  Styrene  gives  ethylcyclohexane,  dipentene 
forms  menthane,  camphene  yields  dihydrocamphene,  bornylene 
gives  camphane,  and  pinene  forms  pinane.  In  the  first  experiments 
with  naphthalene  and  acenaphthene,  tetrahydro-derivatives  were 
obtained.  Since  then,  by  working  at  lower  temperatures,  the  deca- 
hydride  of  naphthalene,  the  tetra-,  octa-,  and  tetradecahydrides  of 
anthracene,  the  di-,  tetra-,  and  dodecahydride  of  phenanthrene,  and 
the  decahydride  of  fluorene  have  been  prepared. 

Aldehydes  and  Ketones.  Aliphatic  aldehydes  and  ketones  with 
nickel  as  catalyst  are  readily  reduced  to  alcohols.  By  this  method 
the  formation  of  pinacones  from  ketones  is  avoided.  Aromatic 
aldehydes  such  as  benzaldehyde  give  benzene  and  carbon  monoxide, 
whilst  aromatic  ketones  give  the  corresponding  hydrocarbons.  The 
diketones,  such  as  benzil  and  benzoin,  also  react  smoothly,  yielding 
dibenzil,  and  the  quinones  are  easily  con  verted  into  the  corresponding 
quinol ;  in  the  case  of  benzoquinone  the  nucleus  may  also  be  reduced, 
and  quinitol  is  formed. 

Phenols.  At  a  temperature  of  215-230°  the  mono-  and  poly- 
hydric  phenols  are  reduced  to  cyclohexanols,  and  a  and  ft  naphthol 
form  the  decahydrides.  If  the  temperature  is  too  high  they 
may  lose  hydrogen,  giving  the  cycloketone.  This  elimination  of 
hydrogen  is  exemplified  in  the  case  of  the  alcohols,  which,  with 
copper  as  catalyst,  form  aldehydes  or  ketones,  and  the  latter  in  turn 
may  lose  carbon  monoxide,  and  finally  pass  into  hydrocarbons. 
An  interesting  example  is  that  of  allyl  alcohol,  which  by  loss  of 


METHOD  OF  SABATIEB  AND  SENDEKENS          167 

hydrogen  is  partly  converted  into  acrolein  and  partly  by  further  re- 
duction into  propionaldehyde.  At  a  lower  temperature  it  is  wholly 
converted  into  propyl  alcohol.  Benzyl  alcohol  yields  benzaldehyde 
at  300°  and  benzene  and  carbon  and  carbon  monoxide  at  380°. 
Furyl  alcohol  is,  however,  reduced  to  methyl  furfurane. 

Unsaturated  Ketones.  In  substances  like  mesityloxide,  the  ethy- 
lene,  but  not  the  ketone,  group  is  reduced ;  unsaturated  cyclic 
ketones,  on  the  other  hand,  can  be  converted  into  cyclohexanols  if 
the  temperature  is  kept  low  and  the  speed  regulated  so  that  a  large 
excess  of  hydrogen  is  present.  In  this  way  pulegone  has  been 
converted  successively  into  pulegomenthone  and  pulegomenthol, 
carvone  into  dihydrocarveol,  and  thujone  into  thujol. 

Unsaturated  Acids  and  Esters  of  the  aliphatic  and  aromatic  series 
are  readily  reduced  to  the  saturated  condition.  Acrylic  acid  is  con- 
verted into  propionic  acid,  oleic  acid  into  stearic  acid,  and  cinnamic 
acid  into  phenylpropionic  acid.  The  esters,  such  as  the  unsaturated 
animal  and  vegetable  oils,  behave  similarly.  The  process  known  as 
'  the  hardening  process '  has  become  of  great  technical  value.  The 
liquid  fish-oils  become  solid  and  the  unpleasant  smell  is  entirely 
removed  on  reduction. 

Acids  and  Anhydrides.  Acetic  acid  passed  over  heated  copper 
at  400°  breaks  up  into  methane,  carbon  dioxide,  and  acetone  ;  with 
zinc  dust  at  250°  it  gives  acetone ;  propionic  acid  and  the  higher 
acids  yield  a  mixture  of  aldehyde  and  ketone  (propionaldehyde 
and  diethylketone).  Acetic  anhydride  with  nickel  breaks  up  into 
acetaldehyde  and  acetic  acid.  The  nucleus  in  aromatic  acids  has 
not  yet  been  reduced  by  this  method.  The  effect  on  phthalic 
anhydride  is  to  give  phthalide. 

N tiro- compounds  are  reduced  to  amines.  Nitrobenzene  passed 
over  copper  at  300°  yields  aniline,  and  other  nitro-compounds  behave 
similarly,  whilst  if  nickel,  the  more  powerful  catalyst,  is  employed, 
the  aniline  breaks  up  into  benzene  and  ammonia.  AJiphatic  nitro- 
compounds  are  less  sensitive  to  nickel,  and  yield  the  amine  at 
150-180°. 

Compounds  such  as  oximes,  cyanides,  isocyanides,  and  isocyanic 
esters,  which  yield  amines  by  other  methods  of  reduction,  are  reduced 
in  the  same  way  by  nickel  and  hydrogen.  With  aliphatic  cyanides 
the  product,  as  a  rule,  is  not  a  single  primary  amine,  but  a  mixture 
with  the  secondaiy  and  tertiary  base,  in  which  the  secondary  amine 
predominates.  The  latter  is  produced  by  union  of  two  or  more 
molecules  of  the  primary  amine,  with  elimination  of  ammonia.  In 
the  case  of  aromatic  cyanides,  cleavage  into  hydrocarbon  and 
ammonia  occurs.  Phenyl  cyanide  gives  toluene  and  ammonia. 


168    CATALYTIC  REACTIONS  OF  ORGANIC  COMPOUNDS 

Isocyanic  esters  and  carbamines  give  secondary  amines,  but  the 
reactions  are  complicated  by  secondary  processes. 

C2H5NCO  +  3H2  =  C2H5NHCH3  +  H20 

C2H5NC  +  2H2     =  C2H5NHCH, 

Like  the  aliphatic  cyanides,  the  aliphatic  aldoximes  give  primary, 
secondary,  and  tertiary  amines,  in  which  the  secondary  amine  pre- 
dominates, whilst  the  cyclic  oximes,  such  as  acetophenonoxime,  give 
in  addition  the  unsaturated  hydrocarbon.  It  is  a  remarkable  fact 
that  the  esters  of  nitrous  acid  yield  amines  on  reduction  just  like 
the  isomeric  nitroparaffins. 

Aromatic  Bases.  The  effect  of  temperature  on  ttie  product  of 
reduction  is  well  illustrated  in  the  case  of  aniline  and  other  aromatic 
bases.  Passed  over  nickel  at  a  high  temperature  aniline  breaks 
up  into  benzene  and  ammonia :  at  190°  it  yields  a  mixture  of 
cyclohexylamine,  dicyclohexylamine  NH(C6H11)2,  and  phenylcyclo- 
hexylamine  C6H5NHC6Hn  ;  at  160-180°  cyclohexylamine  alone  is 
formed,  and  the  homologous  amino  compounds  are  readily  reduced 
in  the  same  way.  Benzylamine,  however,  breaks  up  mainly  into 
toluene  and  ammonia,  with  the  formation  of  little  of  the  cyclohexane 
derivative.  The  only  satisfactory  method  of  obtaining  hexahydro- 
benzylamine  is  to  utilise  the  Sabatier-Senderens  synthesis  of  amines 
by  passing  a  mixture  of  the  alcohol  and  ammonia  over  heated 
thoria.  Though  attempts  to  reduce  pyridine  failed,  the  ring  breaking 
and  giving  rise  to  amylamine,  quinoline  was  converted  into  the 
tetrahydro-derivative  by  reduction  of  the  pyridine  nucleus,  and 
pyrrole  into  pyrrolidine.  Indole,  curiously  enough,  breaks  up  and 
gives  o-toluidine,  and  acridine  forms  <x/?-dimethyl  quinoline,  in 
which  one  benzene  ring  is  opened. 

Halogen  Compounds.  The  general  effect  of  the  process  on 
halogen  compounds  is  either  to  remove  the  halogen,  which  is 
eliminated  as  halogen  acid,  giving  the  unsaturated  hydrocarbon,  or 
simultaneously  to  replace  it  by  hydrogen.  The  aliphatic  mono- 
chloro  compounds  break  up  at  250°  into  hydrogen  chloride  and  the 
olefine ;  2.2  dichloropropane  gives  chloropropylene.  Chloro-  and 
bromo-benzene  lose  halogen  and  yield  benzene. 

Ipatiew's  Method.  The  first  experiments  of  Ipatiew  were 
directed  to  the  study  of  the  pyrogenetic  effect  of  different  catalysts 
at  high  temperatures  (600-800°),  in  the  course  of  which  he  was  able 
to  show  that  a  common  result  of  such  a  process  was  the  removal 
of  hydrogen  and  also  oxygen.  In  this  connection,  iron  and  zinc,  that 


IPATIEW'S  METHOD  169 

is,  easily  oxidisable  metals,  were  found  to  be  peculiarly  active. 
Alcohols  passed  through  iron  'tubes,  or  tubes  containing  zinc,  were 
converted  into  aldehydes  and  ketones,  along  with  olefines  formed 
by  removal  of  water. 

A  variety  of  catalysts,  including  alumina  and  other  metallic  oxides, 
were  examined,  with  interesting  results,  some  of  which  corresponded 
closely  with  those  obtained  by  the  Sabatier-Senderens  process. 
A  novelty  in  the  method  was  afforded  by  the  use  of  hydrogen  at 
high  pressure,  which  was  proved  to  accelerate  the  process.  Ipatiew 
showed,  for  example,  that  ethylene  in  presence  of  alumina  and 
hydrogen  at  a  temperature  of  400-450°  and  at  a  high  pressure 
underwent  polymerisation  and  reduction,  yielding  paraffins.  Acetone, 
which  undergoes  no  change  in  an  iron  tube  at  400°  with  hydrogen 
at  the  ordinary  pressure,  is  converted  at  100  atmospheres  to  the 
extent  of  one-fourth  into  isopropyl  alcohol. 

A  further  development  of  the  method  was  the  action  of  the  two 
oxides  of  nickel1  on  unsaturated  compounds  in  presence  of  hydrogen 
at  a  pressure  of  100-120  atmospheres.  Benzene  was  completely 
reduced  to  cyclohexane  at  250°  in  one  and  a  half  hours,  with  one-tenth 
of  its  weight  of  nickel  oxide,  the  rate  of  reduction  being  therefore 
greater  than  with  the  metal.  Other  aromatic  hydrocarbons,  ketones 
and  bases,  phenols,  terpenes,  and  quinoline  were  reduced  more 
rapidly  than  in  the  Sabatier-Senderens  process,  and,  in  addition,  the 
alkali  salts  of  aromatic  acids  such  asbenzoic,  phthalic,  and  /2-naphthoic 
acids,  which  are  unaffected  by  the  free  metal,  yielded  the  hexa- 
hydro  compounds  in  the  first  two  cases  and  the  tetrahydro  and  deca- 
hydro  acids  in  the  last.  Copper  oxide  can  in  some  cases  replace 
nickel  oxide  with  advantage.2  The  great  difference  in  the  rate  of 
reduction  seems  to  point  to  some  other  action  than  that  of  the  metal 
and  hydrogen.  Ipatiew  explains  the  process  by  supposing  reduction 
of  the  nickel  oxide  to  occur  with  the  formation  of  water,  which 
re-forms  oxide  and  liberates  active  hydrogen. 

Among  reducing  catalysts  should  be  included  metallic  iron  in 
its  action  on  nitre-compounds,  for  it  is  well  known  that  much 
less  than  the  theoretical  amount  of  hydrochloric  acid  is  required  for 
reduction.  The  process  is  explained  by  the  alternate  change  of 
ferrous  chloride  into  the  magnetic  oxide  and  reconversion  into 
ferrous  salt. 

Dehydrogenation.  It  has  already  been  pointed  out  that  the  above 
process,  especially  at  higher  temperatures,  is  reversible,  and  may 

1  Ber.,  1907,  40,  1270,  1281.  *  Ber.,  1909,  42,  2089. 


170    CATALYTIC  EEACTIONS  OF  OKGANIC  COMPOUNDS 

lead  to  the  elimination  of  hydrogen.  Thus  it  has  been  shown  that, 
with  copper  at  250-300°,  the  primary  alcohols  yield  aldehydes,  the 
secondary  alcohols  from  ketones  ;  tertiary  alcohols,  on  the  other  hand, 
give  olefines.  Geraniol  may  be  converted  into  citral,  borneol  into 
camphor,  and  menthol  into  menthone.  Cyclohexanes  pass  into  aro- 
matic hydrocarbons.  Cyclohexanols  above  350°  tend  to  revert  to  the 
phenol,  the  cyclohexylamines  to  the  amino  compounds  ;  the  dodeca- 
hydride  of  anthracene  loses  six  atoms  of  hydrogen  at  200°  and  eight 
atoms  at  260°,  reverting  to  anthracene  at  310°.  At  300°  piperidine 
is  converted  into  pyridine. 

Paraffins  also  lose  hydrogen,  and  apparently  break  down  into  un- 
saturated  groups,  CH3,  CH2,  CH,  which  reunite  to  form  new  saturated 
and  unsaturated  hydrocarbons.  The  results  are  much  the  same  as 
those  obtained  by  Berthelot  by  the  thermal  decomposition  of  the 
paraffins,  but,  in  presence  of  a  catalyst,  are  produced  at  a  much  lower 
temperature. 

Dehydration.  Whilst  metallic  catalysts  are  chiefly  effective  in 
adding  or  removing  hydrogen,  the  metallic  oxides,  such  as  anhydrous 
alumina,  thoria,  the  blue  oxide  of  tungsten  (W205),  and,  as  Ipatiew 
has  shown,  aluminium  phosphate  and  silicate,  possess  a  dehydrating 
action.1  At  temperatures  of  300°  to  350°  the  alcohols  (with  the 
exception  of  methyl  alcohol,  which  gives  methyl  ether)  are  converted 
into  the  corresponding  olefines.  Ethyl  alcohol  forms  ethylene,  and 
borneol  gives  menthene,  &c.  Two  catalysts,  such  as  copper  and 
alumina  or  thoria,  may  thus  produce  essentially  different  reactions, 
for,  with  the  metal,  the  alcohol  loses  hydrogen  and  yields  aldehyde ; 
but  with  the  oxide  it  loses  water  and  gives  the  olefine.  According  to 
Sabatier,1  both  reactions  are  determined  by  a  labile  union  of  the 
catalyst  with  the  compound,  which  differ,  however,  in  the  nature  of 
the  products.  The  action  of  a  dehydrating  and  a  reducing  catalyst 
may  sometimes  be  combined,  so  that  the  olefine  is  first  formed  and 
then  converted  into  the  saturated  hydrocarbon.2  Carvomenthol  has 
been  converted  in  this  way  into  menthane  (Part  III,  p.  230). 

The  dehydrating  action  of  metallic  oxides  can  also  be  accompanied 
by  the  addition  of  other  groups,  and  Sabatier  and  Mailhe3  have 
succeeded  in  preparing  primary  and  secondary  amines  by  passing 
a  mixture  of  alcohol  and  ammonia  over  heated  thoria  at  temperatures 

1  Ipatiew,  Ber.,  1904,  37,  2986  ;    Sabatier  and  Mailhe,  Ann.  Chem.  Phys.,  1910, 
20,  341. 

2  Sabatier  and  Murat,  Compt.  rend.,  1912,  155,  885;  Ipatiew,  Ber.,  1912,  45, 
3205  ;  Ber.,  1911,  44,  2000. 

3  Comp.  rend.,  1911,  153,  160. 


IPATIEW'S  METHOD  171 

between  250°  and  350°.      Thus,  propyl  alcohol  and  ammonia  give 
a  mixture  of  propylamine  and  dipropylamine, 

C3H7OH  +  NH3          =  C3H1NH2  +  H20 
C  H7OH  +  C3H7NH2  =  (C3H7)2NH  +  H2O, 

and  benzyl  alcohol  yields  benzylamine  and  dibenzylamine. 

In  the  same  way  mercaptans  can  be  prepared  by  the  action  of  the 
catalyst  on  a  mixture  of  alcohol  vapour  and  hydrogen  sulphide. 
Ethyl  alcohol,  for  example,  gives  ethyl  mercaptan. 

C2H5OH  +  H2S  =  C2H5SH  +  H.O. 

Esterification  has  also  been  effected  in  a  similar  fashion  by  passing 
the  mixed  vapours  of  alcohol  or  phenol  and  an  organic  acid  over 
a  metallic  oxide.  In  this  last  reaction  titanic  oxide  is  more  effective 
than  thoria.  With  phenols  and  thoria  as  catalyst,  diphenyl  ethers 
are  formed.1 

Finally,  thoria,  alumina,  lime,  and  other  oxides  at  temperatures  of 
350°  and  400°  convert  aliphatic  acids  and  those  aromatic  acids  with 
carboxyl  in  the  side-chains,  such  as  phenyl  acetic  and  phenyl  propionic 
acids,  into  ketones,  whilst  a  combination  of  the  acid  and  formic  acid 
gives  the  aldehyde.  In  the  latter  case  titanic  oxide  is  the  most 
effective  catalyst. 

REFERENCES. 

Ueber  kafalytische  Reduktionen  organischer  Verbindungen,  by  Dr.  A.  Skita.  Enke, 
Stuttgart,  1912. 

Die  Methoden  der  organischen  Chemie,  by  Dr.  B.  Szelinski.     Thieme,  Leipzig,  1911. 

Catalytic  Oxidation.  The  earliest  use  of  catalysts  in  oxidation 
is  to  be  ascribed  to  H.  Davy,  who  used  platinum  in  effecting  the 
union  of  hydrogen  or  marsh  gas  with  oxygen,  a  phenomenon  which 
was  afterwards  utilised  by  Dobereiner  in  his  lamp.  Here  a  jet  of 
hydrogen  was  made  to  impinge  upon  a  surface  of  platinum  upon 
which  oxygen  was  occluded ;  oxygen  combined  with  the  hydrogen, 
raising  the  platinum  to  incandescence  and  bringing  about  ignition  of 
the  jet.  A  later  application  of  platinum  as  an  oxidising  agent  was 
that  by  Hofmann  to  the  preparation  of  formaldehyde,  which  Low 
afterwards  modified  by  replacing  the  platinum  by  copper.  Colloidal 
platinum  or  copper  was  found  to  produce  the  same  effect  when  air 
at  the  ordinary  temperature  was  passed  through  methyl  alcohol  con- 
taining the  metal  in  solution.  Platinum  black  moistened  with 
ethyl  alcohol  and  exposed  to  air  is  converted  into  acetic  acid,  and 

1  Sabatier  and  Mailhe,  Comp.  rend.,  1912,  155,  260. 


172     CATALYTIC  KEACTIONS  OF  ORGANIC  COMPOUNDS 

other  organic  compounds  have  been  oxidised  in  a  similar  fashion. 
Cerous  oxide,  which,  exposed  to  air  in  alkaline  solution,  passes  into 
the  trioxide,  can  bring  about  oxidation,  though  its  use  in  organic 
chemistry  is  restricted.  Vanadium  in  the  form  of  oxide  has  been 
used  along  with  chlorates  in  the  production  of  aniline  black  from 
aniline,  and  the  oxide  of  vanadium  or  ammonium  vanadate  has  also 
been  utilised  in  modifying  the  action  and  increasing  the  yield  of  oxalic 
acid  by  the  action  of  nitric  acid  on  sugar.  But  the  most  interesting 
of  oxidising  catalysts  are  iron  in  presence  of  hydrogen  peroxide,  and 
mercury  or  mercuric  sulphate  in  presence  of  sulphuric  acid. 

The  use  of  hydrogen  peroxide  in  presence  of  a  trace  of  ferrous 
salt  was  introduced  and  studied  by  Fenton1  and  has  proved  an 
invaluable  reagent.  Its  action  was  first  applied  to  the  oxidation  of 
tartaric  acid,  which  is  converted  into  dihydroxymaleic  acid  and  later 
to  that  of  the  polyhydric  alcohols,  which  are  oxidised  mainly  to 
aldoses.  Hydroxy  acids  are  also  readily  attacked,2  yielding  aldehydic 
or  ketonic  acids. 

Kuif 3  modified  the  method  for  preparing  aldoses  by  oxidising  the 
hydroxy  acid  obtained  from  one  sugar,  by  means  of  Fenton's  reagent, 
to  the  lower  aldose  of  the  series  (Part  III,  p.  8). 

It  may  be  added  that  Dakin4  has  shown  that  normal  saturated 
fatty  acids  and  their  phenyl  derivatives  may  be  oxidised  to  /2-hydroxy 
and  /2-ketonic  acids  by  the  action  of  hydrogen  peroxide  on  the  acid 
without  the  addition  of  iron  or  its  salts. 

The  first  example  of  oxidation  by  the  use  of  mercury  in  strong 
sulphuric  acid  was  that  of  naphthalene,  which  at  a  temperature  of 
about  275°  is  rapidly  attacked  and  converted  into  phthalic  acid. 
Anthraquinone  is  converted  by  the  same  process  into  hydroxyanthra- 
quinone,  and  by  protecting  the  hydroxyl  groups  by  esterification 
with  boric  acid  a  hexahydroxyanthraquinone  has  been  formed.  The 
oxidation  of  aniline  is  greatly  accelerated  by  the  presence  of  mercuric 
sulphate  at  275°.  The  use  of  persulphates  in  presence  of  silver 
peroxide  and  silver  nitrate  has  also  been  applied  as  an  energetic 
oxidising  agent,  which  can  convert  benzene  into  quinone.5 

The  catalytic  oxidation  of  enzymes  or  oxidases  is  discussed  in 
Part  III,  chap.  ii. 

Catalytic   Halogenation.     To  complete   the  series  of  catalytic 

1  Trans.  Chem.  Soc.,  1894,  65,  899;  1899,  75,  575. 
»  Trans.  Chem.  Soc..  1900,  77,  69.  s  Ber.,  1898,  31,  1573. 

4  Oxidations  and  Reductions  in  the  Animal  Body,  by  H.  D.  Dakin.     Monographs  on 
Biochemistry  :  Longmans,  Green,  1912. 
e  Kempf,  Ber.,  1905,  38,  3963 ;  Austin,  Trans.  Chem.  Soc.,  1911,  99,  2C4. 


POLYMERISATION  173 

reactions  of  organic  compounds,  mention  should  be  made  of  '  halogen 
carriers',  which  accelerate  in  a  remarkable  degree  the  process  of 
chlorination  and  bromination.  Among  the  more  important  are  iron 
and  its  salts,  the  chlorides  and  bromides  of  antimony,  molybdenum, 
aluminium,  and  phosphorus,  sulphur  and  iodine. 

Catalytic  Condensation,  such  as  the  Friedel-Crafts  reaction,  is 
discussed  under  condensation  (p.  195). 

Polymerisation.  The  term  polymerisation  is  clearly  marked  out 
from  the  process  dealt  with  in  a  succeeding  section  on  condensation 
by  the  nature  of  the  product.  A  polymerisation  product  is  one 
formed  by  the  union  of  two  or  more  molecules  of  the  original  com- 
pound in  such  a  manner  that  depolymerisation,  or  cleavage  into  the 
original  substance,  is  easily  effected.  The  conversion  of  acefcaldehyde 
C2H4O  into  paraldehyde  (C2H4O)3  is  an  example  of  polymerisation, 
for  the  latter  on  distillation  with  a  small  quantity  of  sulphuric  acid 
yields  the  parent  substance.  Aldol  (C2H4O)2,  on  the  other  hand, 
cannot  be  broken  up  readily  into  acetaldehyde.  The  difference  lies 
in  the  nature  of  the  link  between  the  molecules :  in  paraldehyde  it  is 
supposed  to  be  effected  by  means  of  oxygen,  in  aldol  by  means  of 
carbon. 

CH3 


CH3 .  CH(OH) .  CH2 .  CHO 
CH3 .  Hcl      JcH  .  CH3  AldoL 

O 

Paraldehyde. 

The  property  of  undergoing  polymerisation  is  peculiar  to  un- 
saturated  compounds,  from  a  natural  tendency  to  saturate  themselves. 
The  formation  of  diisobutylene  from  isobutylene  under  the  action  of 
sulphuric  acid  or  zinc  chloride  and  that  of  benzene  from  acetylene 
must  be  included  under  condensation  processes  in  accordance  with 
the  definition  adopted  above ;  but  the  conversion  of  aldehydes  into 
the  polymolecular  paraldehydes,  and  the  thio-aldehydes  and  -ketones 
into  trithioaldehydes  and  trithioketones  are  examples  of  polymerisa- 
tion. Polymerisation  of  the  aldehydes  is  effected  by  small  quantities 
of  catalysts,  such  as  mineral  acids  and  certain  metallic  chlorides. 

The  change  is  also  exhibited  by  aromatic  aldehydes  when  acted  upon 
by  alkalis,  but  in  this  case  intramolecular  change  occurs  and  an  ester 
is  formed.  Benzaldehyde  yields  benzyl  benzoate. 

2C6H6CHO  =  CGH5CH2O .  OC .  C6H5. 


174     CATALYTIC  REACTIONS  OF  ORGANIC  COMPOUNDS 

The  only  ketone  which  undergoes  this  change  is  acetone,  which  in 
presence  of  alkali  yields  diacetone  alcohol  CH3.CO.CH2.C(OH).(CH3)2, 
but  breaks  up  on  heating  into  acetone.  The  thio-aldehydes  and 
-ketones  polymerise  so  much  more  readily  than  fche  aldehydes 
that  by  acting  on  the  aldehyde  or  ketone  with  hydrogen  sulphide  in 
presence  of  hydrochloric  acid  polymerisation  occurs  in  process  of 
formation. 

Polymerisation  is  very  commonly  observed  among  cyanogen  com- 
pounds. Cyanogen  itself  yields  paracyanogen  (CN)ft,  hydrocyanic 
acid  in  alkaline  solution  deposits  on  standing  a  brown  amorphous 
compound,  which  is  probably  aminomalonic  nitrile  (CN)2 .  CHNH2, 
whilst  the  alkyl  cyanides  yield  di-  and  tri-molecular  compounds. 
Liquid  cyanogen  chloride  gives  the  solid  tricyanogen  chloride, 
cyanamide  forms  di-  and  tri-cyanamide  (melamine).  Cyanic  acid  and 
its  esters  also  polymerise  readily.  Thiocyanic  acid  behaves  like 
cyanic  acid. 

Light  will  sometimes  effect  polymerisation,  as  in  the  conversion  of 
anthracene  into  dianthracene  (see  Part  II,  p.  149). 


CHAIN  AND  RING  FORMATION 
I.    CONDENSATION,  UNION  OF  CARBON  AND  CARBON 

The  terms  condensation  and  condensation  product  imply  a  process 
and  its  result  which  have  never  been  clearly  defined,  but  which  at 
the  same  time  convey  a  distinct  idea.  Thus,  the  combination  of 
ethyl  alcohol  and  acetic  acid  to  form  an  ester — a  reaction  in  which 
water  is  separated— would  not  be  termed  condensation,  yet  the  union 
of  two  molecules  of  acetaldehyde  to  form  crotonic  aldehyde,  in  which 
water  is  likewise  removed,  would  be  regarded  as  a  typical  example 
of  such  a  process. 

CH3.COOH  +   C2H6OH  =  CH3 .  COOC2H5  +  H20 

Acetic  acid.         Ethyl  alcohol.  Ethyl  acetate. 

CH3 .  CHO  +  CH3 .  CHO  =  CH3 .  CH :  CH .  CHO  +  H2O 

Acetaldehyde.  Crotonic  aldehyde. 

Again,  all  reactions,  of  which  the  conversion  of  aldehyde  into  aldol 
may  be  taken  as  the  type,  are  termed  aldol  condensations,  but  in  this 
case  no  water  is  separated. 

CH3 .  CHO  +  CH3 .  CHO  =  CH3 .  CH(OH) .  CH, .  CHO 

Acetaldehyde.  Aldol. 


CONDENSATION  175 

It  is  easy  to  draw  a  distinction  between  the  formation  of  acetic 
ester  from  alcohol  and  acetic  acid  and  that  of  crotonic  aldehyde  from 
acetaldehyde.  In  the  first  reaction  the  two  molecules  are  linked  in 
the  new  product  by  oxygen  and  are  again  readily  separated  by 
hydrolysis  ;  but  in  the  second  reaction  the  new  linkage  is  established 
between  carbon  atoms,  and  the  product  is  consequently  of  a  much 
more  stable  character.  This  might  help  us  to  a  definition,  were  it 
not  that  in  the  third  example  no  water  is  eliminated,  although  the 
new  combination  is  effected  between  carbon  atoms. 

Although  it  is  true  that  the  formation  of  aldol  is  covered  by  the 
term  polymerisation,  and  should,  strictly  speaking,  be  included  in  this 
category,  yet  it  is  distinct  from  the  process  which  gives  rise  to 
paraldehyde,  a  compound  which,  unlike  aldol,  is  readily  dissociated 
into  the  original  aldehyde.  In  other  words,  the  one  is  a  reversible, 
the  other  is  practically  a  non-reversible  process. 

As  the  formation  of  aldol  is  intimately  linked  with  that  of  crotonic 
aldehyde,  it  would  be  illogical  to  draw  distinctions  between  the  two 
processes,  and  the  term  aldol  condensation  is  therefore  justified. 
-  Condensation  may  then  be  defined  as  the  union  of  two  or  more 
organic  molecules  or  parts  of  the  same  molecule  (with  or  without 
elimination  of  component  elements)  in  which  the  new  combination  is 
effected  between  carbon  atoms. 

If  this  definition  is  accepted  it  will  naturally  embrace  every  kind 
of  reaction  in  which  new  organic  compounds  are  elaborated  by  the 
linking  of  carbon  atoms.  Used  in  this  sense  the  word  condensation 
can  be  conveniently  applied  to  denote  a  certain  section  of  the  more 
comprehensive  categoiy  of  constructive  chemical  changes  which  are 
included  in  the  term  synthesis. 

There  is  no  intention  of  implying  that  the  combination  between 
carbon  atoms  is  subject  to  different  conditions  from  those  obtaining 
among  other  elements.  The  union  is,  as  a  rule,  more  stable,  but  not 
necessarily  so,  and  many  reversible  changes  are  known,  in  which 
carbon  atoms  part  company  as  well  as  combine.  We  shall  see 
presently  that  an  almost  equally  stable  union  may  be  effected  between 
carbon-nitrogen,  carbon-oxygen,  or  carbon-sulphur,  both  in  open 
chain  and  ring  structures. 

It  must  be  recognised,  therefore,  that  the  distinction  is  an  artificial 
one  and  merely  convenient.  Also,  for  convenience,  it  is  desirable  to 
distinguish  between  external  condensation,  in  which  two  or  more 
different  molecules  become  linked  together,  and  internal  condensation, 
in  which  carbon  atoms  in  the  same  molecule  combine,  leading  to 
ring  formation. 


17(5  CHAIN  AND  RING  FORMATION 

The  process  of  condensation  is  connected  with  the  early  history  of 
organic  chemistry  and  was  the  outcome  of  the  first  systematic 
attempts  at  organic  synthesis. 

In  the  following  pages  it  is  intended  to  give  a  general  survey  of 
the  principal  condensation  processes, 

Nature  of  Condensation  Processes.  The  examples  of  condensa- 
tion (of  which  ring  formation  may  be  regarded  as  a  special  case)  are 
so  numerous  and  at  the  same  time  so  varied  in  character  that  it 
would  be  impossible  within  the  limits  of  a  single  chapter  to 
enumerate  them  in  anything  like  detail.  Nevertheless,  it  is  possible 
to  lay  down  certain  broad  generalisations  under  which  the  different 
reactions  may  be  grouped. 

In  the  first  place  it  will  be  observed  that  union  between  molecules 
or  parts  of  a  molecule  is  nearly  always  determined  by  unsaturatioii 
and  by  a  consequent  tendency  for  the  unsaturated  atoms  to  saturate 
themselves.  On  this  basis  condensation  processes  may  be  roughly 
divided  into  two  groups :  those  in  which  the  combining  molecules 
are  induced  to  unite  by  being  rendered,  as  it  were,  artificially 
unsaturated  as  the  result  of  withdrawing  certain  elements,  and  those 
which,  being  already  unsaturated,  combine  either  spontaneously  or 
with  the  help  of  a  reagent  or  catalyst. 

To  the  first  category  belong  those  substances  which,  either  by  the 
action  of  heat  or  oxygen,  lose  hydrogen,  resulting  in  the  union  of 
the  residual  groups.  The  linking  up  of  compounds  by  the  removal 
of  halogen  by  the  aid  of  a  metal  is  illustrated  by  the  processes  of 
Fittig  and  Wurtz  in  chain  formation,  and  by  that  of  Freund  and 
Perkin  in  the  preparation  of  ring  structures.  Condensation  effected 
by  the  separation  of  halogen  acid  through  the  action  of  catalysts  is 
represented  by  the  Friedel-Crafts  method  with  aluminium  and  ferric 
chlorides,  and  by  that  of  Ullmanii  with  finely  divided  copper.  The 
removal  of  carbon  dioxide  by  heating  barium  or  calcium  salts  of 
organic  acids  or  their  anhydrides  and  by  electrolysis  gives  rise  in 
the  first  case  to  ketones  and  in  the  second  to  paraffins  and  new 
homologous  acids. 

It  is,  however,  to  the  second  category,  namely  the  union  of 
unsaturated  compounds,  that  the  largest  number  of  condensation 
processes  belong.  They  may  be  divided  broadly  into  those  in  which 
the  combining  molecules  are  both  unsaturated,  as  in  the  union  of 
acetylene  with  itself  to  form  benzene,  and  those  in  which  one 
molecule  is  saturated  and  the  other  not,  as  in  Michael's,  Reformatsky's, 
and  Grignard's  reactions  (pp.  202-208). 


NATURE  OF  CONDENSATION  PROCESSES          177 

But  the  process  which  has  afforded  the  most  varied  and  extended 
application  is  one  which,  for  want  of  a  better  name,  may  be  termed 
intermolecular  isomeric  change.  In  the  chapter  on  isomeric  change, 
Part  II,  chap,  vi,  the  various  types  of  change  are  enumerated  and 
illustrated.  These  changes  are  brought  about  by  the  wandering  of  a 
hydrogen  atom  from  one  polyvalent  atom  to  another  in  the  molecule, 
accompanied  by  change  of  linkage.  Suppose  a  similar  process  to 
take  place  between  two  polyvalent  atoms  belonging  to  different 
molecules,  such  a  reaction  would  bring  about  mutual  unsaturation, 
resulting  in  a  union  between  them. 

For  example,  the  most  common  case  of  dynamic  isomerism  is 
the  keto-enol  change,  which  .takes  place  when  a  hydrogen  atom 
wanders  from  a  carbon  atom  to  a  neighbouring  oxygen  atom. 

OiC.CH    ^±     HO.C:C 

\    s^  I    /\ 

Now  if  this  change  occurs  between  two  molecules,  one  of  which 

contains  a  CO  group  and  the  other  a  CH2  group,  as  in  the  formation 

of  aldol,  we  have  a  typical  example  of  this  kind  of  condensation, 

0:C  +  CH2    -»     HO.C— CH    ->    C  =  C 

XN    /s.  II  s\      s\ 

a  process  which  may  or  may  not  be  followed  by  the  removal  of 
water  and  the  production  of  an  unsaturated  compound. 

Many  examples  of  similar  intermolecular  isomeric  changes  occur, 
as  for  instance  in  Thorpe's  reaction  (p.  252),  where  the  union  of 
cyanogen  derivatives  with  CH2  groups  takes  place. 
N:C+CH2    -»     HN:C— CH 

I       x-x  II 

Michael's  reaction  might  be  included  in  the  same  category,  corre- 
sponding to  a  shifting  of  the  hydrogen  atom  within  the  molecule  of 
an  unsaturated  hydrocarbon  radical  (see  p.  202). 

CH2  +  CH:CH    ->    CH— CH— CH9 

/Nil  /\          I  I 

If  we  consider  the  various  types  of  isomeric  change  and  the  large 
number  of  compounds  which  they  include,  the  wide  range  and 
variety  of  the  condensation  products  to  which  the  above  process 
may  be  applied  will  be  easily  realised.  At  the  same  time  it  is  restricted 
in  its  application,  being  dependent  mainly  on  the  vicinity  of  certain 
active  (usually  negative)  groups,  and,  to  a  smaller  degree,  on  the 
nature  of  the  condensing  agent.  A  paraffin,  although  it  contains 
numerous  CH2  groups,  does  not  undergo  condensation  of  the  aldol 
type  with  an  aldehyde  or  ketone  under  any  conditions.  Formaldehyde, 

PT.  i  N 


178  CHAIN  AND   RING   FORMATION 

the  most  reactive  of  these  substances,  which  readily  condenses  with 
aromatic  hydrocarbons,  cannot  be  induced  to  combine  with  methane 
or  its  homologues  unless  a  negative  group  such  as  CO,  CN,  NO2 
replaces  at  least  one  atom  of  hydrogen  in  the  paraffin.  The 
acetoacetic  ester  synthesis,  in  which  two  esters  unite  under  the 
influence  of  metallic  sodium  or  sodium  ethoxide,  is  undoubtedly  an 
additive  process,  although  resulting  in  the  separation  of  a  molecule 
of  alcohol.  It  may  be  given  the  following  general  form  : 

/OH 
R.CO.OCH  +  CHX    -»    R.C-CHX > 


R.CO.CH.X  +  C2H5OH 

The  X  in  the  formula  stands  for  an  acid  radical  which  may  be  not 
only  an  ester  group,  but  an  aldehyde,  ketone,  cyanogen,  nitro  or 
imsaturated  ester  or  ketone  group,  HC :  CH .  CO. 

The  aldol  and  benzoin  condensations  and  Claisen  reactions  consist 
in  the  union  of  two  molecules  of  aldehyde,  frequently  followed  by 
the  removal  of  water  and  formation  of  an  unsaturated  aldehyde,  as 
already  explained. 

R.CHO  +  CH.CO    -*    RHC(OH).CH.CO  -*  RHC:C.C:0 

ii  i  i 

Here  again  the  CO  group  in  the  CH2 .  CO  complex  may  be  replaced 
by  carboxyl  (Perkin's  reaction),  carbethoxyl,  and  the  other  negative 
groups  mentioned  above,  whilst  the  aldehyde  may  be  substituted 
by  a  ketone  (Claisen's  and  Knoevenagel's  reactions,  pp.  238,  241). 

Ring  Formation.  Nearly  all  the  above  reactions  may  become 
intramolecular  if  the  necessary  grouping  is  present,  and  in  such 
cases  ring  formation  follows.  But  the  process  in  some  cases  is 
subject  to  certain  limitations,  which  depend  on  the  number  of  atoms 
composing  the  ring.  The  acetoacetic  ester  synthesis,  for  example, 
may  be  applied  intramolecularly  to  adipic,  pimelic,  and  suberic  esters, 
but  not  to  glutaric  or  succinic  esters. 

CH2 .  CH2 .  COOC2H5  CH2 .  CH2 

>CO  +  C2H5OH 


1 


.  CH2 .  COOC2H5  CH2 .  CH .  COOR 

In  other  words,  it  is  possible  to  form  a  5,  6,  and  7  carbon  ring, 
but  not  one  of  three  or  four  carbon  atoms. 

Baeyer's  Strain  Theory.     The  commonest  type  of  cyclic  com- 
pounds occurring  in  nature  are  those  consisting  of  5  or  6  atoms. 


BAEYEE'S   STRAIN   THEORY  179 

and,  as  a  matter  of  experience,  they  are  of  all  ring  structures  the 
most  readily  produced,  and  the  most  stable  under  the  action  of  heat 
and  reagents. 

An  ingenious  and  veiy  plausible  explanation  has  been  advanced 
by  Baeyer  under  the  name  of  the  Strain  (Spannung)  Theory,  which 
is  based  upon  stereochemical  considerations.  Supposing  the  four 
valencies  of  carbon  to  be  directed  towards  the  solid  angles  of  a 
regular  tetrahedron,  they  will  make  angles  of  109°  28'  with  ono 
another.  Any  distortion  or  deviation  of  these  valency  directions 
will  lead,  according  to  the  theoiy,  to  a  condition  of  strain  which  will 
make  itself  evident  by  loss  of  stability,  and  the  greater  the  strain 
the  greater  the  instability. 

Baeyer  regards  an  olefine  as  the  first  member  of  the  cyclic  series, 
in  which  the  normal  position  of  the  two  bonds  uniting  the  carbon 
atoms  is  assumed  to  be  bent  so  as  to  form  straight  parallel  links 
between  the  atoms.  The  amount  of  distortion  can  be  estimated,  for 
each  bond  is  bent  inwards  through  half  the  total  angle  which  the 
two  make  with  one  another,  £(109°  28')  =  54°  44';  in  a  cyclopro- 
pane derivative,  in  which  the  carbon  atoms  may  be  supposed  to 
make  an  equilateral  triangle,  the  amount  of  displacement  will  be 
|  (109°  28' -60°)  =  24°  44'.  The  amount  of  deviation  from  the 
normal  is  given  in  the  following  table  : 

Cycloethane  (Ethylene)         i  (109°  280  54°  44' 

Cyclopropane  |(  109°  28'  -CO0)  24°  44' 

Cyclobutane  \  (109°  28'  -90°)  9°  44' 

Cyclopentane  £  (109°  28'  -108°)  0°  44'- 

Cyclohexane  £  (109°  28'  -120°)  -5°  16V 

Cycloheptane  £  (109°  28'  - 128°  34')         -  9°  33'- 

Cyclooctane  |  (109°  28'  - 135°)  - 12°  46' 

It  will  be  seen  that  the  condition  of  greatest  strain  will  occur 
in  the  olefine,  that  of  least  strain  in  the  cyclopentanes,  and  then  in 
the  cyclohexanes.  In  the  last  three  the  strain  will  be  outwards 
instead  of  inwards. 

Stability  of  Ring  Structures.  We  will  now  consider  briefly  to 
what  extent  the  experimental  facts  harmonise  with  Baeyer 's  theory. 
It  should  be  stated  at  the  outset  that  the  theoiy  has  reference  to 
cycloparaffins  and  their  derivatives,  but  does  not  necessarily  include 
aromatic  compounds  or  heterocyclic  systems,  which  will  be  considered 
separately ;  for  the  unsaturated  nature  of  the  aromatic  nucleus  and 
the  presence  of  other  atoms  than  carbon  in  the  ring  may,  and 
probably  do,  affect  the  stability  of  the  system.  No  great  importance 
need  therefore  be  attached  to  an  observation  such  as  that  of 
Markownikoff,  who  found  that  a  cyclopentane  derivative  on 

N2 


180  CHAIN  AND   RING  FORMATION 

bromination  in  presence  of  aluminium  bromide  is  converted  into 
a  brominated  benzene. 

At  the  same  time  it  is  a  significant  fact  that  among  heterocyclic, 
as  well  as  homocyclic  compounds,  5  and  6  atom  rings  are  not  only 
most  easily  prepared,  but  of  commonest  occurrence  among  natural 
products  derived  from  animal  and  plant  organisms.  Although  there 
are  certain  facts  not  in  harmony  with  the  theory,  which,  as  Aschan  l 
says,  cannot  be  elevated  to  the  position  of  a  law,  like  the  theory  of 
Van't  Hoff  and  Le  Bel,  it  nevertheless  presents  a  rough  picture 
of  molecular  mechanics,  which  has  had  the  effect  of  stimulating 
inquiry  and  enriching  the  science  with  fruitful  results.  In  studying 
the  stability  of  the  cycloparaffins  and  their  derivatives,  it  is  important 
to  remember  that  this  property  varies  with  the  nature  of  the  radicals 
attached  to  the  cyclic  carbon  atoms.  Kotz,2  who  made  a  careful 
study  of  the  subject,  found  that  the  stability  of  the  cyclopropane 
ring  is  diminished  by  the  introduction  of  alkyl  groups  and  increased 
by  that  of  carboxyl,  and  Biichner 3  has  shown  that  the  latter  effect 
is  further  enhanced  when  the  carboxyl  groups  are  attached  to  different 
carbon  atoms.  For  example,  cyclopropane  1,1,  dicarboxylic  acid 
undergoes  disruption  in  contact  with  hydrobromic  acid  in  the  cold, 

CH2 

/\  ->    CH2Br.CH2.CH(C02H)2 

H.C— C(C02H)2 

whereas  the  1 .  2  dicarboxylic  acid  is  not  affected  even  when  boiled 
with  the  concentrated  reagent.  The  effect  of  carboxyl  on  the  stability 
of  3-  and  4-carbon  rings  is,  in  short,  so  great  that  frequently  more 
depends  on  the  nature  and  position  of  the  radicals  than  on  the 
number  of  carbon  atoms  in  the  ring.4 

We  will  consider  first  the  stability  of  the  different  cycloparaffins 
towards  reagents,  then  the  facility  with  which  they  are  formed,  and 
finally  their  conversion  into  one  another. 

Action  of  Reagents.  Taking  ethylene  as  representing  the  first 
member  of  the  cyclic  series,  it  is  characterised  by  the  ease  with 
which  it  unites  with  halogens,  halogen  acids,  strong  sulphuric  acid, 
and  undergoes  oxidation  with  permanganate.  These  properties, 
which  are  manifested  in  the  hydrocarbon  itself,  may  be  modified  to 
a  greater  or  less  extent,  as  we  have  seen  (p.  116),  in  certain  of  its 

1  Chemie  der  alicyklischen  Verbindungen,  by  0.  Aschan.     Vieweg,  Brunswick,  1905. 

8  J.  prakt.  Chem.,  1903,  68,  156.    "  3  Annalen,  1895,  284,  198. 

4  Perkin  and  Simousen,  Trans.  Chem.  Soc.,  1907,  01,  817;  Perkin  and  Golds- 
worthy,  Trans.  Chem.  Soc.,  1914,  105,  2665 ;  Kenner,  Trans.  Chem.  Soc.,  1914,  105, 
2685. 


ACTION   OF   REAGENTS  181 

derivatives.  Cyclopropane  combines  with  bromine  in  sunlight, 
though  not  so  readily  as  benzene,  to  form  trimethylene  bromide  ; 
it  unites  quite  readily  with  hydrobromic  and  hydriodic  acids,  giving 
normal  propyl  bromide  and  iodide,  and  with  sulphuric  acid,  forming 
propyl  hydrogen  sulphate,  which  on  heating  with  water  is  converted 
into  w-propyl  alcohol.  In  all  these  reactions  it  resembles  ethylene, 
but  differs  in  its  indifference  towards  permanganate,  which  is  without 
action.  Cyclopropane  is  decomposed  above  550°  (or,  as  Ipatiew1 
found,  at  100°  by  passing  it  through  a  tube  filled  with  iron  filings) 
and  gives  propylene.  Dimethylcyclopropane  is  completely  converted 
into  trimethylethylene  when  passed  over  alumina  at  350°. 


(CH3)2C|         ->    (CH3)2.C:CH.CH3 
^CH2 

Cyclobutane  is  inert  towards  halogens,  halogen  acids,   sulphuric 
acid,  and  permanganate,  and  is  unaffected  by  heat.    Cyclobutanol  is, 
however,  converted  by  hydrobromic  acid1  into  1  .  3  dibromobutane,2 
H,C  _  CH2  H2C       CH2  CH2Br    CH3 


H2C      CHOH  H2C      CHBr  CH2 CHBr 

and   truxillic  acid   breaks   up   on   heating  into   two   molecules   of 
cinnamic  acid  : 

C6H5CH— CH .  COOH  C6H5CH  :  CH .  COOH 

I         I  -•> 

C6H5CH— CH .  COOH  C6H5CH  :  CH .  COOH 

Truxillic  acid.  Cinnamic  acid. 

but  in  these  cases  the  stability  of  the  ring  is  modified  by  the  presence 
of  radicals. 

In  cyclopentane  and  cyclohexane  and  their  derivatives  ring 
cleavage  is  never  effected  by  any  of  the  reagents  mentioned  above, 
unless  the  ring  is  already  weakened  by  the  attachment  of  oxygen  to 
carbon  in  the  form  of  ketone  groups. 

Increasing  stability  of  the  ring  up  to  five  and  six  atoms  of  carbon 
is  also  proved  by  the  heat  of  combustion,  which  is  discussed  at  greater 
length  in  a  later  chapter  (Part  II,  p.  68).  It  is  there  shown  that  the 
heat  of  combustion  decreases  from  ethylene  to  cyclohexane,  indicating 
increasing  stability  or  decreasing  energy  content.  Stohmann  and 
Kleber  compared  the  mean  difference  between  the  heats  of  com- 
bustion of  the  cycloparaffins  and  the  paraffins,  allowing  for  the  two 

1  Ber.,  1902,  35,  1063  ;  1903,  36,  2014. 

2  Perkin,  Trans.  Chem.  Soc.,  1894,  65,  951. 


182  CHAIN  AND  RING  FORMATION 

additional  hydrogen  atoms  in  the  open-chain  compound,  the  results 
of  which  are  given  in  calories  in  column  I,  whilst  the  mean  loss  of 
energy  is  given  in  column  II. 

I         II 
cals.       cals. 

Cycloethane  (ethylone)          33-1        35-9 
Cyclopropane  37-1        31.9 

Cyclobutane  39-9        29.1 

Cyclopentano  16-1        52-9 

Cyclohexane  14-3        51-7 

Evidence  of  Ring  Formation.  It  is  well  known  that  certain 
general  reactions  which  lead  to  the  formation  of  5  and  6  atom  rings 
fail  when  it  is  attempted  to  produce  smaller  or  larger  ring  structures. 
The  acetoacetic  ester  synthesis  when  applied  to  glutaric  ester  is  a  case 
in  point  (p.  178).  Similarly  calcium  adipate,  pimelate,  and  suberate 
yield  respectively  cyclopentanone,  cyclohexanone,  and  cycloheptanone 
(p.  226),  whereas  calcium  succinate  gives  in  place  of  cyclopropanone 
a  cyclic  diketone  of  the  double  formula l 

CH2.CO.CH2 

CH2.CO.CH2 

Perkin 2  found,  from  his  method  of  using  sodium  malonic  ester  and 
a  dibromoparaffin  in  ring  formation  (p.  192),  that  whilst  the  5-carbon 
ring  is  produced  almost  quantitatively,  the  4- carbon  ring  is  found 
in  smaller  quantity  and  a  still  smaller  yield  of  the  3- carbon  ring  is 
obtained.  The  6-carbon  ring  also  gave  a  poorer  yield  than  the 
5-carbon  ring,  whilst  the  7-carbon  ring  was  prepared  under  con- 
siderable difficulty. 

Another  interesting  fact  of  the  same  order  is  the  action  of  zinc  on 
a/?8-tribromobutane  dicarboxylic  acid,  which  might  form  either 
a  cyclopropane  or  cyclobutane  derivative.3  It  is  exclusively  the 
second  reaction  which  occurs. 

CH2Br  CH2 

COOH  .  CBr/  .CHBr .  COOH          COOH  .  CBr/\CH  .  COOH 


CH2  CH2 

An  observation  pointing  in  the  same  direction  was  made  by  Thorpe 
and  Campbell 4  in  the  case  of  cyclopropane  and  cyclobutane  cyanacetic 
esters,  the  former,  under  the  action  of  sodiocyanacetic  ester,  giving 
an  open  chain  condensation  product,  whereas  the  cyclobutane  deriva- 
tive combined,  but  preserved  the  ring  intact. 

1  Feist,  Ber.,  1895,  28,  731.  2  Ber.,  1902,  35,  2105. 

3  Perkin  and  Simonsen,  Trans.  Chem.  Soc.,  1909,  95,  1169. 
«  Trans.  Chem.  Soc.,  1910,  97,  2418. 


TRANSFORMATION  OF  KING  SYSTEMS  183 

Experiments  have  been  carried  out  by  Thorpe,  Beesley,  and  Ingold  l 
to  ascertain  which  of  the  two  types  of  compound,  I  or  II,  would  more 
easily  form  a  cyclopropane  ring. 


Nc/ic 


yvv  109°  28' 
X! 
II. 

For  if  cyclohexane  represents  a  regular  hexagon,  the  endocyclic 
angles  must  be  120°,  thereby  changing  the  angle  which  the  exocyclic 
carbon  atoms  make  with  the  cyclic  carbon  from  109°  28'  (the  normal 
angle)  to  107°  16'.  It  follows,  therefore,  from  Baeyer's  theory  that 
type  I,  where  the  carbon  atoms  are  in  closer  proximity,  should  yield 
a  three-carbon  ring  more  readily  than  type  II. 

The  two  substances  submitted  to  experiment  were  a-bromocyclo- 
hexane  diacetic  ester  representing  type  I  and  a-bromo-/?/?-dimethyl 
glutaric  ester  corresponding  to  type  II. 

TT  /i         r*TT  • '•  : 

H20 ^2  CHJBriCOJR  CH 

HC  V 

CO,R 

2  /2  : :  : : 

The  result  clearly  indicated  that  by  removal  of  hydrogen  bromide 
type  I  gave  a  more  easily  formed  and  more  stable  ring  than  type  II. 

Transformation  of  Ring  Systems.  One  of  the  most  interesting 
features  of  this  problem  is  the  evidence  of  stability  furnished  by  the 
change  of  one  ring  system  into  another. 

The  work  of  Zincke  and  Hantzsch  on  the  action  of  chlorine  in 
alkaline  solution  on  the  phenols  and  other  aromatic  compounds  has 
afforded  numerous  examples  of  the  change  of  a  6-carboii  ring  into 
a  5-carbon  ring.  We  may  take  the  case  of  ordinary  phenol  which 
passes  into  a  derivative  of  cyclopentane. 

C(OH) 

,CH  C12C C(OH) .  COOH 


HC/ 


Most  of  the  other  phenols  behave  in  a  similar  fashion.2  Wreden 
found  that  when  benzene  is  reduced  with  hydriodic  acid  at  300°,  it 
yields  a  hydrocarbon  CGH12,  which  was  first  mistaken  for  cyclo- 
hexane, but  its  low  boiling-point  (70°)  and  its  conversion  into 

1  Trans.  Chem.  Soc.,  1915,  107,  1080. 

8  Meyer- Jacobson,  Lehrbuch  der  organischen  Chemie,  vol.  ii,  part  i,  p.  32. 


184  CHAIN   AND   KING   FORMATION 

a  mixture  of  glutaric,  succinic,  and  acetic  acids  on  oxidation  left  no 
doubt  as  to  its  identity  with  methylcyclopentane.  Zelinsky  also 
found  that  cyclohexanol,  on  reduction  with  hydriodic  acid,  gives 
a  mixture  of  cyclohexane  and  methylcyclopentane.  Aschan  has 
since  shown  that  cyclohexane  changes  to  methylcyclopentane  on 
simply  heating  in  a  closed  tube  with  or  without  aluminium  chloride. 
A  reaction  of  the  same  kind  is  the  conversion  of  suberyl  iodide  with 
hydriodic  acid  into  methylcyclohexane  and  dimethylcyclopentane. 
Cyclobutylcarbinol  and  hydrogen  bromide  give  cyclopentyl  bromide.1 

HC. CH.CH9OH 

+  HBr 


— 2~j 
HC 


Cyclobutylcarbinol.  Cyclopentyl  bromide. 

In  all  these  cases  it  may  be  taken  that  there  is  a  change  from  the 
less  to  the  more  stable  ring  system. 

Examples  of  the  conversion  of  a  4-carbon  ring  to  a  5-carbon  ring 
are  also  furnished  by  pinene,  which  with  hydrogen  chloride  passes 
readily  into  bornyl  chloride,  that  is,  from  a  bridged  ring  of  4  carbon 
atoms  to  one  of  5  (see  Part  III,  p.  219). 

Certain  exceptions  must  be  recorded.  Demjanow2  found  that 
by  the  action  of  nitrous  acid,  cyclobutylmethylamine  is  converted 
into  cyclopentanol  and  by  loss  of  water  into  cyclopentene.  This 
reaction  is,  however,  capable  of  converting  a  larger  into  a  smaller 
system ;  for  when  cyclobutylamine  is  acted  upon  with  nitrous  acid, 
it  yields  a  mixture  of  cyclobutanol  and  cyclopropylcarbinol. 

CH.NH2  H2CV      CH2OH 

l\  I 
•Orlo  Id  n\j OH 


H0o 


Cyclopentylmethylamine  gives  with  the  same  reagent  cyclohexyl 
alcohol  and  cyclohexylmethylamine  is  converted  into  suberyl  alcohol. 
Wallach 3  explains  the  latter  reactions  by  assuming  the  formation 
of  an  intermediate  labile  double-ring  structure,  which  undergoes 
hydrolysis. 

CH2 — CH2\  CH2 — CH2v  ^TT 

|  >CH.CH2NH2    -»      |  X          +N- 

CH2— CH/  CH2-  CH  ^— ^CH2 

H20    CH2 — CH2 — CH2 

CH2.CH(OH).CH2 

1  Demjanow,  Chem.  Soc.  Abstr.,  1910,  1,  888. 

8  Chem.  Soc.  Abstr.,  1903,  1,  403.  3  Annalen,  1907,  £53,  331. 


TRANSFORMATION   OF   RING   SYSTEMS  185 

Further,  cyclopentyl  nitrite,  obtained  by  the  action  of  silver  nitrite 
on  cyclopentyl  iodide,  yields,  when  treated  with  concentrated  alkali, 
nitro-methylcyclobutane,1 

CH2-CH2X  CH2-C(CH,)N02 

>CH.ONO        ->         | 
CH2— CH/  CH2— CH2 

Cyclopentyl  nitrite.  Nitro-methylcyclobutane. 

from  which  it  appears  that  cyclic  compounds  without  side-chains 
pass  into  smaller  rings  with  side-chains,  whereas,  if  a  side-chain  is 
present  in  the  original  compound,  the  tendency  is  to  form  a 
larger  ring. 

In  concluding  this  account  of  the  conditions  which  determine 
the  formation  of  the  cycloparaffins,  a  description  of  the  preparation 
of  some  of  the  simpler  members  of  the  group  is  appended. 

The  preparation  of  cyclopropane  is  described  under  Wurtz's 
method  (p.  188),  and  was  first  effected  by  Freund.  Like  propane  it 
is  a  gas.  Methylcyclobutane  was  prepared  by  Perkin  by  the  method 
above  referred  to  ;  cyclobutane  itself  was  obtained  by  Willstatter 2  by 
a  method  which  he  has  successfully  applied  to  the  preparation  of 
other  cycloparamns  and  which  requires  a  little  explanation.  Cyclo- 
butanecarboxylic  acid,  obtained  from  the  dicarboxylic  acid  (prepared 
by  Perkin),  by  heating  is  converted  into  the  amide,  which  by 
Hofmann's  reaction  is  transformed  into  the  atnine.  From  this,  on 
methylation,  cyclobutyltetramethylammonium  hydroxide  is  formed, 
which  on  distillation  loses  trimethylamine  and  water  and  yields 
cyclobutene.  The  latter  is  finally  reduced  by  the  Sabatier-Senderens 
process  (p.  164). 

CH2— CH .  CO .  NH2  CH2— CH .  NH, 

CH2— CH2  CH2— CH2 

CH2— CH .  N(CH3)3OH  CH.,— CH 

->     |          ||     +  H20  +  N(CH3)3 
CH2-CH2  CH2-CH 

Cyclobutene. 

Cyclopentane  was  first  prepared  by  Wislicenus  from  cyclo- 
pentanone  by  reduction  (p.  189).  Cyclohexane  was  obtained  in  the 
same  way  from  cyclohexanone  by  Zelinsky,3  from  cyclohexadione 
by  Baeyer  (p.  225),  and  by  Perkin  from  hexamethylenedibromide 

1  Rosanoff,  Chem.  Soc.  Abslr.,  1915,  i.  657. 

2  Ber.,  1905,  38,  1992. 

8  Ber.,  1895,  28,  780 ;  1901,  34,  2799. 


186  CHAIN  AND  EING  FORMATION 

(p.   192).     It  has   also  been   obtained  by  tho   direct   reduction  of 
benzene  (p.  163). 

Cycloheptane  has  been  prepared  by  Markownikow l  from  suberic 
acid  by  Wislicenus'  method,  that  is,  by  conversion  into  the  ketone  and 
reduction  in  the  same  manner  as  cyclopentane  (p.  200).  It  has  also 
been  prepared  from  the  ketone  by  conversion  into  the  oxime  and 
reduction  to  the  amine  by  Willstatter,2  who  used  the  method  applied 
in  the  case  of  cyclobutane. 

CH2 .  CH2  .  CO  CH2  .  CII2 .  C  :  NOH       CH2 .  CH2 .  CH  .  NH2 

CH2  — >  CH2       — * 

r*TT       r*Ti  r<TT       r*u      I^TT  r»ir       I^TT       r<tr 

.  v^H2 V^il2  \jtt-2 \J"-z  •  l>'»*8  V^±12 — vy-t!2 — ^-H-2 

Cyclo-octane  has  also  been  prepared  by  Willstatter 3  and  Veraguth 
from  pseudopelletierine  by  exhaustive  methylation.  Pseudopelle- 
tierine is  an  alkaloid  found  in  pomegranate  and  is  related  to  tropinone 
(Part  III,  p.  318).  On  reduction  it  yields  N-methyl  granatinine. 

CH9-  CH CH2  CH2— CH CH2 


CHf 


io 


CH2    NCH3    CO      -»     CH2    NCH3     CH2 

III                   III 
CH2— CH CH2  CH2— CH CH2 

Pseudopelletierine.  N-methyl  granatinine. 

On  methylation  the  bridge  is  broken  and  the  following  substance 
is  formed,  which  on  distillation  loses  water  and  trimethylamine  and 
gives  a-cyclo-octadiene. 

N(CH3)3OH 

CH2— CH-  CH2  CH2— CH=CH 

[2  CH2       -+    CH2  CH2 

I  I  I  I 

CH2-CH=CH  CH2-CH=CH 

Cyclo  octadiene. 

This  compound  rapidly  polymerises,  but  if  converted  into  the  di- 
hydrobromide  and  hydrobromic  acid  removed  with  quinoline,  a  second 
more  stable  /2-cyclo-octadiene  is  formed,  which  on  reduction  by 
the  Sabatier-Senderens  method  gives  cyclo-octane.  Cyclononane 
has  been  prepared  by  Zelinsky 4  by  Wislicenus'  method  from  sebacic 
acid  by  distillation  of  the  calcium  salt  and  conversion  into  the  cyclic 
ketone. 

1  J.  Russ.  phys.  Chem.  Soc.}  1893,  25,  364.  2  Ber.,  1908,  41,  148. 

3  Ber.,  1907,  40,  957.  *  Ber.,  1907,  40,  3277. 


TRANSFORMATION   OF  RING  SYSTEMS 


187 


The  following  are  the  boiling  points  of  the  cycloparaffins  and  the 
corresponding  olefines  and  paraffins  : 


Number  of 
carbon  atoms. 

Olefine. 

Paraffin. 

Cyclo- 
paraffin. 

3 

-48° 

-35° 

-45° 

4 

-5° 

+  12° 

+  1° 

5 

+  40° 

49° 

30° 

6 

69° 

81° 

69° 

7 

95° 

117° 

98° 

8 

122° 

146° 

126° 

9 

171° 

150° 

REFERENCE. 
Chernie  der  alicyklischen  Verbindungen,  by  O.  Aschan.     Vieweg,  Brunswick,  1905. 

Group  1.     Condensation  by  separation  of  Elements. 

Removal  of  Hydrogen.     Under  the  action  of  heat  and  certain 
reagents    condensation    may    take    place   with    loss   of    hydrogen. 
Benzene  passed  through  a  hot  tube  is  converted  into  diphenyl. 
2C6H6  =  C6H5.C6H5  +  H2. 

Diphenyl  methane  yields  fluorene,  and  stilbene  is  converted  into 
phenanthrene.  Isobutylene  when  heated  with  strong  sulphuric  acid 
yields  a  mixture  of  isomeric  diisobutylenes  ;  but  this  reaction  is 
no  doubt  brought  about  by  the  alternate  addition  and  removal  of 
sulphuric  acid  rather  than  by  the  direct  elimination  of  hydrogen.1 

yCH3 
(CH3)2C  :  CH2  +  H2S04  =  (CH3)2  .  C< 

\S04H 


(CH3)2C  :  CH2 


r^TT 

2C/       '    =  (CH3)2C:CH.C(CH3)3  +  H2S04 
XSO4H 

Hydrogen  may  also  be  removed  and  condensation  induced  by  the 
action  of  oxidising  agents.  An  illustration  of  the  process  is  afforded 
by  the  linking  of  two  indoxyl  (thioindoxyl  or  bromindoxyl)  groups 
in  alkaline  solution  in  presence  of  atmospheric  oxygen,  to  form 
indigo  and  its  derivatives, 

CO  CO  CO  CO 

/~i  TT  s~i  Tj  /    xr*       r*/    \r<  TI 

>UGhL4  -       CGhl4<^^>O  =  O<^^>O6H4 

[H  NH  NH 

Indoxyl.  Indigo. 


NH 


1  Butlerow,  Annalen,  1877, 189,  65. 


188  CHAIN   AND  KING  FOKMATION 

The  use  of  oxidising  agents  is  usually  more  effective.  Dimethyl- 
aniline,  for  example,  when  oxidised  with  sulphuric  acid  and  lead 
peroxide  is  converted  into  tetramethyldiaminodiphenyl  and  the 
formation  of  magenta  from  a  mixture  of  o-  and  p-toluidiiie  and 
aniline  may  be  cited  as  a  similar  case  of  condensation. 

Removal  of  Halogens.  It  was  in  the  pursuit  of  the  free  radicals 
that  Frankland  first  used  potassium  and  the  alkyl  cyanides,  which 
in  1849  he  replaced  by  zinc  and  the  alkyl  iodides  (p.  35). l  This 
inquiry  resulted  in  two  discoveries  of  the  highest  importance — 
the  synthesis  of  the  paraffins  and  the  production  of  the  first  organo- 
metallic  compounds.  The  method  devised  by  Frankland  of  using 
a  metal  to  remove  the  halogen  from  an  organic  halogen  compound,  so 
as  to  effect  a  union  between  the  residual  parts  of  the  molecules,  has 
undergone  a  wide  extension. 

The  Method  of  Wurtz.  In  1855  Wurtz 2  introduced  sodium  in 
place  of  zinc  for  preparing  different  paraffins  from  the  alkyl  iodides, 
as,  for  example,  butane  from  ethyl  iodide, 

2C2H5I  +  2Na  =  C4H10  +  2NaI 

and  the  same  method  was  applied  by  Fittig3  in  1863  to  the  prepara- 
tion of  the  homologues  of  benzene : 

C6H5Br  +  CH3I  +  2Na  =  C6H5  .  CH3  +  NaBr  +  Nal 
Bromobenzene.  Toluene. 

In  1868  Wislicenus4  employed  finely  divided  metallic  silver  in 
the  synthesis  of  dibasic  from  monobasic  acids. 

CH2.CH2.COOH 

2CH.J.CH2.COOH  +  2Ag  =  |  +  2AgI 

CH2  .  CH2 .  COOH 

/8-Iodopropionic  acid.  Adipic  acid. 

Finely  divided  copper,  although  occasionally  used  in  place  of  silver, 
has  only  received  extended  application  as  a  condensing  agent  in 
recent  years5  (see  p.  199). 

The  formation  of  benzoic  ester  by  Wurtz  from  bromobenzene, 
chloroformic  ester,  and  sodium, 

C6H6Br  +  C1COOC2H6  +  2Na  =  C6H5COOC2H5  +  NaBr  +  Nad 
and  that  of  sodium  benzoate  from  bromobenzene,  carbon  dioxide,  and 
sodium  by  Kekule 6  are  merely  modifications  of  the  same  process  : 
CaH6Br  +  CO,  +  2Na  =  CcII5COONa  +  NaBr 

1  Phil  Trans.,  1852,  142,  417  ;  Annalen,  1853,  85,  329. 

2  Annalen,  1855,  96,  365.  3  Annalen,  1863,  131,  304. 
*  Annalen,  1868,  149,  221  ;  Ber.,  1869,  2,  720. 

6  Ullmann,  Ber.,  1903,  36,  2383 ;  1904,  37,  853  ;  Annalen,  1904,  332,  38 ;  Ber.. 
1905,  38,  729,  2120,  2211.  6  Annalen,  1866,  137,  180. 


THE  METHOD  OF  WURTZ  189 

The  same  principle  has  been  applied  by  Freimd '  to  the  production 
of  ring  compounds  by  internal  condensation  in  the  synthesis  of 
cyclopropane  from  trimethylene  bromide  and  sodium  or  zinc, 


CH2Br  CH2 

2         +  Na2  =  CH 


\ 


+  2NaBr 


CH2Br  CH2 

and  by  Perkin,  jun.,2  and  his  collaborators  in  the  synthesis  of  methyl 
cyclobutane  from  1 .  4  dibromopentane, 

CH2— CHBr .  CH3         CH2— CH  .  CH3 

+  Na2=  |  +  2NaBr 

CH2— CH2Br  CH2-CH2 

and  cyclohexane  from  hexamethylene  dibromide, 

CH2— CH2— CH2Br  CH2— CH2— CH2 

|  +  Na2  =  |  |       +  2NaBr 

CH2 — CH2 — CH2Br  CH2 — CH2 — CH2 

Removal  of  Sodium  by  Halogens  and  Halogen  Compounds. 
The  Method  of  Wislicenns.  The  discovery  of  a  series  of  organic 
compounds  of  the  nature  of  1 .  3  diketones,  such  as  acetylacetone, 
acetoacetic  ester,  malonic  ester,  acetone  dicarboxylic  ester,  and 
similarly  constituted  compounds,  such  as  cyanacetic  ester,  benzyl 
cyanide,  desoxybenzoin,  &c.,  which  form  sodium  compounds  by  the 
replacement  of  hydrogen  by  sodium,  gave  a  new  impulse  to  the  study 
of  organic  synthesis.  The  further  discovery  by  Conrad s  that  in  the 
preparation  of  the  sodium  compounds  metallic  sodium  or  dry  sodium 
ethoxide  could  be  replaced  by  an  alcoholic  solution  of  sodium 
ethoxide  added  greatly  to  the  convenience  of  the  method.  We  are 
not  concerned  for  the  moment  either  with  the  structure  of  the 
sodium  compounds,  which  has  been  discussed  under  tautomerism 
(Part  II,  chap,  vi),  or  with  the  mechanism  of  the  formation  of  the 
compounds  themselves,  which  finds  a  place  under  the  acetoacetic 
ester  synthesis  (p.  222).  Our  attention  at  present  will  be  directed 
to  the  description  of  a  few  of  the  more  important  synthetic  operations 
in  which  the  sodium  compounds  have  been  utilised. 

Before  doing  so,  it  will  clear  the  ground  in  connection  with  this 
and  many  other  reactions  to  be  subsequently  described,  if  the  condi- 
tions which  determine  the  mobility  of  a  hydrogen  atom  in  a  hydro- 


1  Monatsh.,  1882,  3,  C25. 

2  Trans.  Chem.  Soc.,  1888,  53,  201 ;  1894,  65,  590. 

1880,  240,  127. 


190  CHAIN  AND  RING  FORMATION 

carbon  (CH2)  group  are  more  carefully  defined.  As  a  rule  the 
proximity  of  a  negative  group  produces  this  effect ;  but  in  a  varying 
degree,  depending  partly  on  the  strength  of  the  negative  group,  partly 
on  that  of  the  metal  or  metallic  compound  used.  Acetone,  in  which 
one  CO  group  is  present,  does  not  react  with  sodium  ethoxide,  though 
it  forms  a  sodium  compound  with  metallic  sodium.  A  phenyl 
group  enhances  the  mobility  and  acetophenone  C6H5 .  CO .  CH3  is 
more  reactive,  but  here  again  sodium  ethoxide  is  without  action.  If, 
however,  sodamide  be  substituted  and  the  product  acted  on  with  an 
alkyl  iodide,  the  three  hydrogen  atoms  of  the  methyl  group  may  be 
replaced  successively  by  alkyl  groups.1  The  presence  of  a  phenyl, 
cyanogen,  carbethoxyl,  or  an  ethylene  group  produces  much  the 
same  effect  as  a  carboxyl  group.  A  nitro  group  may,  on  the  other 
hand,  determine  the  formation  of  a  sodium  compound.  In  all  these 
cases  the  presence  of  a  second  negative  group  will  produce  the 
required  mobility  of  the  hydrogen  atom,  which  seems  necessary  to 
produce  a  sodium  compound.  Consequently,  reactivity  is  manifested 
(1)  by  the  1  .  3  dike  tones  with  the  group  CO  .  CH2 .  CO,  which  includes 
esters  like  malonic  ester,  (2)  by  compounds  with  the  group 
CO  .  CH2 .  CN,  such  as  cyanacetic  ester,  (3)  by  those  with  the  group 
CO.CH2.C6H5,  like  phenylacetic  ester  and  desoxybenzoin,  (4)  by 
substances  such  as  CGH5 .  CH2 .  CN,  and  (5)  finally  by  compounds 
which  contain  an  ethylene  linkage  CO .  CH2 .  CH  :  CH,  such  as 
glutaconic  ester  C6H-OOC .  CH2 .  CH :  CH  .  COOC2H5,  which  can  be 
methylated  by  the  action  of  sodium  ethoxide  and  methyl  iodide, 
yielding  a  mono-  and  dimethyl  derivative.2 

We  will  now  turn  to  the  various  reactions  in  which  the  formation 
of  a  metallic  derivative  enables  the  above  group  of  compounds  to 
participate.  If  to  an  alcoholic  solution  of  these  compounds  contain- 
ing the  equivalent  of  one  atom  of  sodium,  an  alkyl  iodide  is  added 
and  the  liquid  boiled  until  neutral,  sodium  iodide  separates  and  the 
alkyl  derivative  is  formed.  The  process  may  usually  be  repeated  by 
adding  a  second  atomic  equivalent  of  sodium  in  alcohol  and  a  second 
molecule  of  alkyl  iodide,  when  the  dialkyl  derivative  is  obtained. 
If  these  sodium  compounds  possess,  as  they  admittedly  do,  the 
enolic  structure,  the  action  of  the  alkyl  iodide  must  be  represented 
by  some  such  general  schemes  as  the  following,  in  which  addition 
precedes  substitution  (see  p.  124).8 

1  Haller  and  Bauer,  Compt.  rend.,  1909,  148,  70. 

2  Henrich,  Ber.,  1898,  31,  2103. 

3  Michael,  J.  prakt,  Chem.,  1892,  46,  194;  1899,  60,  316;  Annalen,  1891,  268, 
67,  113;  1892,  270,  330;  Thorpe,  Trans.  Chem.  Soc.,  1900,  77,  923. 


THE   METHOD   OF  WISLTCENUS  191 

—  C(ONa)  =  CH—  =    -CO.CHR—  +  Nal 

:         + 

i          K 

and  —  C(ONa)  =  CR—   =   —  CO  .  CR2—  +  Nal 

:        + 

I  E 

It  will  be  seen  that  the  negative  iodine  unites  with  the  positive 
sodium  and  the  positive  radical  with  the  carbon  which  forms  part 
of  a  negative  group.1  It  should  be  noted  in  passing  that  by  substi- 
tuting pyridine  for  sodium  ethoxide  as  condensing  agent,  the  alkyl 
attaches  itself  to  the  oxygen  and  the  isomeric  enolic  form  is  produced. 

The  use  of  these  methods  for  synthesising  acids  and  ketones  from 
acetoacetic  ester,  and  acids  from  malonic  and  cyanacetic  ester,  belongs 
to  the  elementary  facts  of  organic  chemistry  and  need  not  be  dis- 
cussed in  detail. 

If,  in  place  of  an  alkyl  iodide,  iodine  is  added  to  the  alcoholic 
solution  of  the  sodium  compounds,  polybasic  acids  may  be  obtained 
from  acetoacetic  ester  and  malonic  ester  as  follows  :  2 

2CH3  .  CO  .  CH2  .  COOC2H5  +  2C2H5ONa  +  12 

Acetoacetic  ester. 

CH3  .  CO  .  CH  .  COOC2H5 
CH3  .  CO  .  CH  .  COOC2H5 

Diacetosuccinic  ester. 

2CH2(COOC2H5)2  +  2C2H5ONa  +  12 

Malonic  ester. 

CH(COOC2H5)9 

=  |  " 

CH(COOC2H5)2 

Ethane  tetracarboxylic  ester. 

This  method  9  has  been  used  in  the  preparation  of  a  cyclohexane 
derivative  by  acting  upon  the  disodium  compound  of  acetone  dicar- 
boxylic  ester  with  iodine. 

2C,H5OOC  .  CHNa  .  CO  .  CHNa  .  COOC2H5  +  2I2  +  4C2H5ONa 

C2H5OOC.CH   CO 


=  C2H5OOC  .  HO  CR  .  COOC2H5 


H.COOC2H5 

Again,  if  a  halogen  derivative  of  a  fatty  ester  like  chloracetic  ester 


1  This  view  is  embodied  in  Michael's  '  positive-negative'  theory  (see  p.  114). 

2  Harrow,  Annalen,  1880,  201,  142  ;  Bischoff  and  Rach,  Ber.,  1S84,  17,  2781. 
8  v.  Pechmann,  Ber.,  1897,  30,  2569. 


192  CHAIN  AND   KING  FORMATION 

is  allowed  to  interact,  a  variety  of  polybasic  acids  may  be  prepared, 
which  the  following  examples  will  serve  to  illustrate : * 

CH3COCH2COOC2H5  CH3COCHCOOC2H5 

+  NaOC9H5  =  +  NaCl  +  C0H5OH 

-f  C1CH2COOC2H5  CH2COOC2H5 

Acetosuccinic  ester. 

CH2(COOC2H5)2  CH(COOC2H6)2 

+  NaOC2H5  =  |  +  NaCl  4-  C2H5OH 

+  C1CH2COOC2H5  CH2COOC2H5 

Ethenyl  tricarboxylic  ester. 

Chloroformic  ester  is  an  exception  to  the  general  rule  in  producing 
mainly  the  enolic  ester, 

/OCO.OC2H5 
CH3 .  C/ 

N3H .  COOC2H5 

Cyanacetic  ester  behaves  in  precisely  the  same  way  as  malonic  ester. 
To  take  one  example,  symmetrical  dimethylsuccinic  ester  has  been 
prepared  as  follows  : 2 

By  the  combined  action  of  cyanacetic  ester,  a-bromopropionic  ester, 
and  sodium  ethoxide,  cyanomethyl  succinic  ester  is  first  obtained. 
^CN  CH3  CN  CH3 

CH2   +BrCH    +NaOC2H5  =  CH CH   +  NaBr  +  C,H5OH 

II  II 

COOC2H5  COOC2H5  COOC2H5  COOC2H5 

The  substance  is  then  boiled  up  with  methyl  iodide  and  sodium 
ethoxide,  when  the  following  change  occurs  : 
CN            CH3                                             CH3    CH3 
H I^H   +  CH  x  +  NaQC  H        CN  \c ^      Nal  +  0  H  QH 

II  I         \ 

COOC2H5  COOC2H5  C2H5OOC        COOC2H5 

Finally,  the  product  is  hydrolysed  with  hydrochloric  acid,  whereby 
the  cyanogen  group  is  converted  into  carboxyl  and  removed  as  carbon 
dioxide,  yielding  symmetrical  dimethylsuccinic  acid. 

The  Synthesis  of  Cyclic  Compounds  (Perkin's  Method).  The 
formation  of  sodium  compounds  of  1 . 3  diketones,  more  especially 
of  malonic  and  acetoacetic  ester,  has  found  a  further  important 
application  in  the  production  of  cyclic  compounds.3  The  subject 
can  only  be  briefly  outlined. 

1  Bischoff  and  Each,  Annalen,  1882,  214,  88  ;  1886,  234,  36  ;  Conrad,  Anndlen, 
1877, 188,  218. 

8  Bone  and  Sprankling,  Trans.  Chem.  Soc.,  1899,  75,  839. 
'  W.  H.  Perkin,  jun.,  Her.,  1902,  35,  2091. 


i 


THE   SYNTHESIS  OP  CYCLIC  COMPOUNDS        193 

Ethylene  bromide  and  sodium  malonic  ester  give  cyclopropane 
dicarboxylic  ester. 

CH2Br  /COOC2H5 

I  +  CH<  +  2NaOC2H5 

CH2Br  "XCOOC2H5 

CH2X       xCOOC2H5 

=  |        >C<  +2NaBr  +  2C2H5OH 

CH/     XJOOC2H6 

The  product  when  hydrolysed  gives  the  dibasic  acid,  and,  on 
heating,  the  corresponding  monobasic  acid. 

In  a  precisely  similar  fashion  trimethylene  bromide,  pentamethy- 
lene  bromide,  and  o-xylylene  bromide  have  been  converted  into  cyclic 
compounds  having  the  following  structure  : 

CH2  H2C  _  j'    2 

CH2/\C(COOC2H5)2  CH2/~~\C(COOC2H5)2 

CH2  H2C       CH2 

CH2 

C6H4/\C(COOC2H5)2 

CH2 

From  each  of  these  the  corresponding  di-  and  mono-basic  acids 
have  been  prepared. 

Cyclic  formation  may  also  be  effected  in  the  following  way  : 
ethylene  chloride,  malonic  ester,  and  sodium  ethoxide  yield,  in 
addition  to  the  cyclopropane  compound  already  described,  an  open- 
chain  ester. 

CH2C1    CH2(COOC2H5)2  CH2.CH(COOC2H5)2 

+  +  2NaOC2H5=j  +2NaCl 

CH.C1    CH2(COOC2H5)2  CH2.CH(COOC2H5)2 

If  this  butane  tetracarboxylic  ester  is  converted  into  the  disodium 
compound  and  then  treated  with  bromine  or  iodine,  ring  formation 
occurs. 

CH2  .  CNa(COOC2H5)2  CH2—  C(COOC2H5)2 

+  Br2  =  |  +  2NaBr 

CH2  .  CNa(COOC2H5)2  CH2—  C(COOC2H5)2 

In  place  of  ethylene  chloride  trimethylene  bromide  may  be  used 
when  cyclopentane  tetracarboxylic  ester  is  formed. 

2  .  CH(COOC2H3)2  /CH2-C(COOC2H5)2 

—  >       CH 


2  .  CH(COOC2H5)2  CH2—  C(COOC2H3)2 

PT.  I  O 


194  CHAIN  AND  RING  FORMATION 

Furthermore,  by  introducing  methylene  iodide  in  place  of  iodine 
in  the  last  reaction,  a  cyclohexane  derivative  is  obtained. 

,CH2 .  CNa(COOC2H5)2  ,CH2— C(COOC2H5)2 

CH2  +  CII2I2  =  CH2          \CH2  +2NaI 

\CH2 .  CNa(COOC2H5)2  \CH2— C(COOC2H5)2 

Each  of  these  tetracarboxylic  esters  may  be  converted  into  dicarb- 
oxylic  acids  by  the  usual  process  of  hydrolysis  and  heating. 

The  above  series  of  reactions  when  applied  to  acetoacetic  ester, 
benzoylacetic  ester,  or  acetone  dicarboxylic  ester  gives  a  somewhat 
different  result. 

Ethylene  bromide,  acetoacetic  ester,  and  sodium  ethoxide  yield 
not  only  acetylcyclopropane  carboxylic  ester,  in  which  the  action 
proceeds  normally  as  in  the  case  of  malonic  ester,  but  the  enolic 
form  of  acetoacetic  ester  also  comes  into  play,  giving  an  inner  ether, 
methyldehydropentone  carboxylic  ester. 

CH2X      /CO .  CH3  CH2— 0— C  .  CH3 

I      ><  I  || 

CH/     \COOC2H5  CH2 C.COOC2HC 

Acetylcyclopropane  Methyldehydropentone 

carboxylic  ester.  .,         carboxylic  ester. 

In  the  case  of  trimethylene  bromide,  the  second  reaction  proceeds 
to  the  complete  exclusion  of  the  first.  On  hydrolysis  of  the  above 
esters,  the  acid,  which  is  formed,  loses  carbon  dioxide  on  heating  and 
gives  the  following  products  : 

CH2— 0-C.CH3 
.CO.CH3 

CH2—    —  CH 

Removal  of  Hydrogen  Chloride.  Many  halogen  compounds 
condense  directly  with  other  organic  compounds  on  heating,  with 
the  elimination  of  hydrogen  chloride.  Benzyl  cyanide  and  fluorene 
unite  in  this  way  with  benzophenone  dichloride : 

5\CH2  +  C^C/       5  =          >N>C  :  C/       5  +  2HC1 
CN/  \C6H5         CN/         XC6H5 

|  °    4N>CH2  +  C12C/        5  =  | 6    'Nc  :  C/        "  +  2HC1 
CCH/  \C6H5      C6H/          \C6H5 

Carbonyl  chloride  combines  with  dimethylaniline, 

XCCH4N(CH3)2 

COC12  +  2CCH6N(CH3)2  =  C0<  +  2HC1 

\CCH4N(CH3)2 


REMOVAL   OF  HYDROGEN   CHLORIDE  195 

and  benzotrichloride  forms  a  derivative  of  triphenylmethane  with 

phenols. 

/C6H4OH 
C6H5CC13  -f  2C6H5OH  =  C1C<-C6H4OH  +  2HC1 


Beimer-Tiemann  Reaction.1  In  this  reaction  chloroform  and 
carbon  tetrachloride  unite  with  phenols  in  presence  of  caustic  soda 
solution  or  sodium  ethoxide,  giving  hydroxyaldehydes  in  the  first 
case  and  hydroxy  acids  in  the  second. 

With  ordinary  phenol  a  mixture  of  o-  and  jp-hydroxybenzaldehyde 
are  formed. 

/ONa 
CGH5OII  +  CHC13  +  4NaOH  =  C6H4<  +  3NaCl  +  3H2O 


With  ordinary  phenol  and  carbon  tetrachloride,  the  ^compound 
is  the  main  product. 


, 

CCH5OH  +  CC14  +  5NaOH  -  C6H4<  -f  4NaCl  +  3H9O 

\COONa 

The  Friedel-Crafts  Reaction.  The  reaction,  discovered  in  1877 
by  Friedel  and  Crafts,9  in  which  anhydrous  aluminium  or  ferric 
chloride  are  the  active  agents,  has  had  an  extraordinarily  wide  and 
varied  application  in  organic  synthesis.  It  is  connected  more 
particularly  with  the  union  of  aromatic  hydrocarbons  and  their 
derivatives  with  a  variety  of  other  organic  compounds,  such  as  alkyl 
halides,  acid  chlorides,  &c.  Hydroxyl  and  amino  groups,  if  present 
in  the  nucleus,  must  be  protected  by  converting  the  former  into  an 
ether  and  the  latter  into  an  acetyl  derivative.  Nitro  compounds  do 
not  react. 

Hydrocarbons  can  be  obtained  by  combining  an  alkyl  halide,  e.  g. 
methyl  chloride,  with  benzene  in  presence  of  anhydrous  aluminium 
chloride,  when  a  vigorous  evolution  of  hydrogen  chloride  occurs  and 
toluene  is  formed. 

C6H6  +  CH3C1[  +  A1C13]  =  C6H5  .  CH3  +  HC1 

Ketones  can  be  prepared  in  the  same  way  by  using  an  aromatic 
hydrocarbon  and  an  acid  chloride.  Benzene  and  acetyl  chloride  give 
acetophenone. 

C6H6  +  CH,  .  COC1[  +  A1C13]  =  C6H5  .  CO  .  CH3  +  HC1 

According  to  V.  Meyer3  a  second  acetyl  group  can  only  be  intro- 

1  Bar.,  1876,  9,  1285. 

8  C,,mpt.  ren<1.,  1877,  84,  1392  ;  Ann.  Chim.  Phys.,  1884,  ;6),  1.  506. 

3  Ber.,  1896,  29,  847,  1413,  2568. 

o  2 


196  CHAIN  AND  RING  FORMATION 

duced  if  both  lie  between  two  ortho  methyl  groups  as  in  mesitylene. 
If,  in  place  of  acetyl  chloride,  chloracetyl  chloride  is  substituted, 
a  third  radical  is  readily  introduced.1 

Carbonyl  chloride  and  benzene  react  in  a  similar  manner. 
2C6H6  -f  COC12[  -f  A1C13]  =  C6H5  .  CO .  C6H5  +  2HC1 

Aldehydes  have  been  obtained  by  uniting  an  aromatic  hydrocarbon 
with  a  mixture  of  carbon  monoxide  and  hydrogen  chloride  in 
presence  of  dry  cuprous  chloride  and  aluminium  chloride.2 

p-Tolylaldehyde  has  been  prepared  from  toluene. 

yCH3 

C6H5 .  CH3  +  HC1 .  CO  =  C6H4<  -f  HC1 

\CHO 

A  better  method  was  subsequently  found  for  obtaining  the  alde- 
hydes of  phenols  and  phenol  ethers  by  the  use  of  the  compound  of 
hydrogen  chloride  and  hydrogen  cyanide.  HCN .  HC1  is  prepared 
in  situ  by  passing  the  mixed  gases  into  the  phenol  ether  and 
aluminium  chloride.  The  imino-compound,  which  is  formed,  is 
acidified  with  hydrochloric  acid  and  distilled  in  steam,  when  the 

aldehyde  passes  over. 

yOCH3 

CCH5OCH3  +  C1CH  :  NH[  +  A1C13]  =  C6H4<  +  HC1 

\CH  :  NH 

/OCH3  /OCH3 

C6H4<  +  H20  =  C6H4<  +NH3 

\CH :  NH  XCHO 

Aldoximes  are  obtained  by  combining  chloroformaldoxime  with 
phenols3  or  aromatic  hydrocarbons  with  mercury  fulminate,4  the 
first  reaction  taking  place  as  follows : 

/OH 

C6H5OH  +  C1CH  :  NOH  =  C6H4<  +  HC1 

\CH:NOH 

and  the  second,  in  presence  of  a  little  aluminium  hydrate,  according 
to  the  following  equation,  which  gives  a  yield  of  seventy  per  cent, 
of  syn-aldoxime : 

C6H6  +  C  :  NOH  =  C6H5CH  :  NOH 

From  both  compounds  aldehydes  are  readily  obtained  t  by 
hydrolysis. 

Acids  can  be  prepared  either  by  the  action  of  carbonyl  chloride  in 

1  Ber.,  1901,  34,  1826. 

2  Gattermann  and  Koch,  Ber.,  1897,  30,  1622  ;  Annalen,  1906,  347,  347 ;  1907, 
357,  313. 

3  Scholl,  Ber.,  1901,  34,  1441. 

4  Scholl,  Ber.,  1899,  32,  3493  ;  1903,  36,  10,  322. 


THE   FKIEDEL-CRAFTS   REACTION  197 

the  proportion  required  to  give  the  acid  chloride,  which  is  then 
hydrolysed, 

C6H6  +  COC12[  +  A1C13]  -*  C6H5COC1  -*-  C6H5COOH 

or  by  the  action  of  chloroformamide,  which  is  obtained  by  heating 
cyanuric  acid  in  a  current  of  hydrogen  chloride,  the  vapours  being 
then  passed  directly  into  the  hydrocarbon  containing  aluminium 
chloride.  The  amide  of  the  acid  is  finally  hydrolysed. 

C6H6  +  C1CONH2[  +  A1C13]  =  CCH5CONH2  +  HC1 

Vorlander  ]  has  succeeded  in  condensing  benzene  with  cyanogen, 

C6H6  +  (CN)2  =  C6H5C(CN):NH 

which  yields  benzoyl  cyanide  on  hydrolysis. 

Aluminium  chloride  has  also  been  used  by  Kipping 2  for  effecting 
internal  condensation  in  the  case  of  phenylpropionyl  chloride  and 
phenylvaleryl  chloride,  in  which  ring  formation  occurs,  the  first 
giving  rise  to  hydrindone,  and  the  second  to  benzocyclo-heptanone.3 

CH2 

C6H5.CH2.CH2.COC1    -»    C6H4<^>CH2 

CO 

CH2  CH2 

C6H5 .  CH2 .  CH2 .  CH2 .  CH2 .  COC1    ->    C6H4/~     ~\CH2 

CO~CH2 

Combes,4  by  acting  on  butyryl  chloride  with  aluminium  chloride, 
obtained  a  cyclohexane  derivative. 

CO    CH.C2H5 
3C3H7COC1    ->    C2H5.HC/~      ^>CO 

CO    CH.C2H5 

In  most  of  the  foregoing  reactions  a  halogen  compound  is  used  in 
conjunction  with  the  hydrocarbon,  and  hydrogen  chloride  is  evolved. 
But  aluminium  chloride  can  also  act  as  a  condensing  agent  by  virtue 
of  its  dehydrating  action,  and  in  other  ways.  Thus,  phthalic 
anhydride  and  benzene  condense  to  o-benzoylbenzoic  acid  :5 

/COOH 


/co\ 
C.H  /    >o 

NXK 


<X).C0H5 


1  Ber.,  1911,  44,  2455.  »  Trans.  Chcm.  Soc.,  1894,  65,  484. 

3  Kipping  and  Hall,  Proc.  Chem.  Soc.,  1899,  15,  173. 

*  Compt.  rend.,  1894,  118,  1336.        6  Heller  and  Schiilke,  Bcr.,  1908,  41,  3627. 


198  CHAIN  AND   RING   FORMATION 

Phenylcarbimide  combines  to  form  benzanilide, 

C6H6  +  CO :  NC6H5[  +  A1C13]  =  C6H, .  CO  .  NH .  C6H5 
and  sulphur  dioxide  produces  benzene  sulphinic  acid. 
C6H6  +  S02[  +  A1C13]  =  C6H5 .  S02H 

Reactions  similar  to  the  above  can  also  be  carried  out  with  an- 
hydrous ferric  chloride,  and  in  some  cases,  as  in  the  union  of  benzene 
with  benzyl  chloride,  a  minute  quantity  of  zinc  or  copper  in  powder, 
or  the  aluminium-mercury  couple,  will  effect  condensation. 
CCH6  +  C1CH2 .  CCH5  =  C6H5 .  CH2 .  CGH5  +  HC1 

Diphenylmethaiie. 

It  should  be  pointed  out  that  the  aluminium  chloride  occasionally 
reverses  the  process  of  condensation,  for  Jacobsen1  has  shown  that  if 
hexamethylbenzeno,  to  which  a  small  quantity  of  aluminium  chloride 
is  added,  is  heated  in  a  current  of  hydrogen  chloride,  methyl  groups 
are  successively  detached,  with  the  formation  of  penta-,  tetra-,  &c., 
niethylbenzenes,  and,  finally,  benzene.  Another  interesting  fact 
connected  with  the  reaction  is  the  transference  of  methyl  groups 
from  one  hydrocarbon  to  another  under  the  influence  of  this  reagent. 
Anschutz  and  Immendorff 2  obtained  from  toluene  both  benzene  and 
m-  and  ^-xylene. 

Various  theories  have  been  advanced  to  explain  these  curious 
changes.  Friedel  and  Crafts  assumed  the  formation  of  an  intermediate 
compound,  C6H5 .  A12C15,  which  unites  with  the  alkyl  halide, 
regenerating  aluminium  chloride. 

CGH5 A12C15  -f  C2H5C1  =  CCH5 .  C2II6  -f  A12C18 

This  would  represent  the  chloride  as  a  true  catalyst,  in  which 
a  small  quantity  would  be  sufficient  to  bring  about  the  union  of  an 
indefinite  amount  of  the  reacting  mateiials.  In  practice,  this  is  not 
usually  the  case,  for  it  is  found  that  the  amount  of  product  increases 
approximately  with  the  quantity  of  reagent.  As  Steele 3  has  pointed 
out,  this  fact  does  not  necessarily  preclude  the  action  of  the 
aluminium  chloride  as  a  catalyst,  provided  it  can  be  shown  that  it 
forms  a  stable  compound  with  the  product.  The  observations  of 
Gustavson 4  and  others  seem  to  point  in  this  direction. 

Gustavson  5  isolated  a  number  of  definite  compounds  of  aluminium 
chloride  and  hydrocarbon,  and  aluminium  chloride,  alkyl  halide  and 
hydrocarbon  (possessing  such  formulae  as  A12C1(- .  6CGHG,  and  with 
ethyl  chloride  A1,C1, .  CGH,(C2H,)3 .  GCGHG),  which  appear  to  act  as 
catalysts. 

1  Ber.,  1885,  18,  339.     2  Ber.,  1885,  18,  G57.     3  Trans.  Chcm.  Soc.,  1903,  83,  1490. 
4  Compt.  rend.,  1903,  136,  1065 ;    1905,  140,  940  ;  J.  W.  Walker  and  Spencer, 
Trans.  Chem.  Soc.,  1904,  85,  1106.  5  Ber.,  1878,  11,  2151. 


THE  FRIEDEL-CRAFTS  REACTION  19y 

More  recently  Menschutkin,  Pfeiffer,  and  others  have  succeeded  in  preparing 
a  variety  of  carbon  compounds  of  metallic  chlorides,  which  may,  under  appro- 
priate conditions,  possess  a  similar  function.  Slator  found  that  in  the  chlorina- 
tion  of  benzene  in  presence  of  stannic  and  ferric  chloride  the  velocity  is 
proportional  to  the  concentration  of  the  catalyst.  Godschmidt  and  Larsen 
have  arrived  at  a  similar  result.  From  a  study  of  the  condensation  of  anisole 
with  benzyl  chloride  they  find  the  reaction  to  be  unimolecular,  and  that  the 
aluminium  chloride  acts  as  a  catalyst  increasing  the  velocity  in  proportion  to 
its  concentration.  Steele  concludes  from  similar  observations  l  that  the  action 
of  aluminium  and  ferric  chlorides  in  inducing  the  Friedel-Crafts  reaction  differs 
from  many  cases  of  true  catalysis  only  in  the  accident  that  these  reagents 
combine  with  certain  substances  produced  during  the  reaction,  and  are  thus 
removed  from  the  system '.  There  are  thus  two  processes  at  work — an  activating 
process  produced  by  the  co-ordination  of  the  catalyst  with  the  original  compound 
and  a  retarding  action  caused  by  the  withdrawal  of  the  catalyst  in  combination 
with  the  product.  Both  processes  seem  to  follow  from  the  researches  of  Olivier 
and  B6s.eken  on  the  interaction  of  jj-bromobenzenesulphonyl  chloride  and 
benzene  in  that  the  aluminium  chloride  appears  to  be  reactive  only  to  the 
extent  to  which  it  is  combined  with  the  acid  chloride,  and  part  of  the  catalyst 
is  removed  in  union  with  the  product  of  the  reaction.  In  spite  of  this  fact  the 
speed  of  the  reaction  is  increased  by  an  excess  of  free  aluminium  chloride,  and 
cannot  therefore  be  ascribed  entirely  to  the  co-ordinated  compound  of  the 
catalyst. 

Ullmann's  Method.  Finely  divided  copper,  although  occasionally 
used  in  former  years  in  place  of  silver,  has  recently  been  introduced 
by  Ullmann  and  received  extensive  and  important  applications  as 
a  condensing  agent.1  The  metal  can  be  prepared  by  adding  zinc 
dust  to  a  solution  of  copper  sulphate  and  carefully  washing  and 
drying  the  precipitate,  but  the  commercial  copper-bronze  or  finely 
divided  metal,  prepared  mechanically,  is  better.  The  method  is  gener- 
ally employed  for  removing  halogens  from  the  benzene  nucleus.  For 
example,  iodobenzene  is  converted  almost  quantitatively  at  230°  into 
diphenyl;  bromotoluene  in  the  same  way  gives  ditolyl.  Bromo- 
benzene  and  chloracetic  ester  when  heated  with  finely  divided  copper 
to  180-200°  are  converted  into  phenylacetic  ester.  The  reaction,  in 
certain  cases  at  least,  is  catalytic.  Ortho-chlorobenzoic  acid  reacts 
with  glycocoll  to  form  phenylglycine-o-carboxylic  acid ;  but  the 
process  is  greatly  accelerated  by  the  addition  of  a  minute  quantity 
of  copper  powder.  Similarly,  a  phenyl  radical  can  be  introduced 
into  the  ammo  group  of  amino  acids  and  amides.  By  heating  the 
potassium  salt  of  anthranilic  acid  with  bromobenzene  and  a  little 
copper,  phenylaminobenzoic  acid  is  formed. 

,NH2  /NHC0H5 

CCH/  +BrC0H,  =     CCH4<  +KBr 

XJOOK  \COOH 

Potassium  anthranilate.  Phenylaminobenxoie  acid. 

i  Btr.,  1901,  34,  2174,  3802  ;  1903,  30,  2383  ;  1904,  S7,  853  ;  1905,  38,  729, 
21  JO  ;  1'JOG,  30,  1691,  2211.  Annaien,  1904,  332,  38;  1906,  350,  83. 


200  CHAIN   AND   RING  FORMATION 

Phenyl  iodide  will  also  react  with  sodium  phenate  when  a  trace 
of  copper  is  present,  although  in  its  absence  not  one  per  cent,  of 
diphenyl  ether  is  produced. 

C6H5ONa  +  IC6H5  =  C6H5OC6H3  +  Nal 

The  above  examples  have  been  selected  to  illustrate  the  varied 
application  of  the  method,  which  has  proved  to  possess  considerable 
technical  importance. 

Removal  of  Carbon  Dioxide.  The  well-known  method  of  forming 
ketones  by  the  distillation  of  calcium  salts  of  organic  acids  has  been 
utilised  by  J.  Wislicenus  l  for  the  preparation  of  cyclic  ketones  by 
employing  the  calcium  salts  of  dibasic  acids.  For  this  purpose, 
adipic,*  pimelic,  suberic,8  azelaic  and  sebacic  acids  4  have  been  used, 
giving  cyclic  ketones  containing  5,  6,  7,  8  and  9  carbon  atoms. 

CH2  .  CH2  .  COOV  CH2  .  CH2 

I  >a      -        | 

CH2.CH2.(XXK  CHa.CHj 

From  these  compounds  the  corresponding  cycloparaffins  may  be 
obtained  by  reduction  to  the  alcohol,  conversion  into  the  iodide,  and 
reduction  of  the  iodide  with  zinc  and  acetic  acid. 


>Ca      »        |  >CO  +  CaC03 

CH9. 


-- 

>CHOH  -*  I  >CHI  -»  I  )CH9 

CH2.CH/  CH2—  CH/  CH2—  CH/ 

Cyclopentanol.  Cyclopentane. 

The  above  method  of  distilling  the  calcium  salts  may  be  modified 
in  certain  cases  with  advantage  by  converting  the  dibasic  acid  into 
the  anhydride  and  heating  the  latter.5  The  process  of  electrolysis 
may  also  effect  condensation  by  removal  of  carbon  dioxide  and 
hydrogen.  By  way  of  illustration  the  following  example  may  be 
taken,  in  which  sodium  ethyl  succinate  is  converted  into  adipic  ester. 

CH2  .COOC2H5  CH2  .  CH2  .  COOC2H5 

2  |  =|  +Ha  +  2COo 

CH2  .  COONa(H)  CH2  .  CH2  .  COOC2H5 

The  application  of  the  method  in  this  way  to  the  synthesis  of  the 
higher  dibasic  acids  was  first  used  by  Crum-Brown  and  Walker,6 


1  Annalen,  1893,  275,  309. 

2  Montemartini,  Gazz.  chim.  ital,  1896,  26,  275. 
8  Blanc,  Compt.  rend.,  1907,  144,  1356. 

*  Derlon,  Ber.,  1898,  31,  1962. 

6  Blanc,  Compt.  rend.,  1907,  144,  1356. 

•  Annalen,  1890,  261,  107 ;  Trans.  Ck-em.  Soc.,  1896,  60,  1278. 


KEMOVAL  OF  CARBON  DIOXIDE  201 

and  has  since  been  studied  by  v.  Miller,1  and  v.  Miller  and  Hofer, 
who  electrolysed  mixtures  of  organic  and  inorganic  salts. 

The  following  examples  may  serve  to  illustrate  the  reactions: 

CH3 .  CH2 :  COOK     =     CH,CH2I  +  CO,  +  2K 

I    :  K 

CH3 .  CH2  ;  COONa     =     CH, .  CH2NO2  +  C02  -f  2Na 
N02  I  Na 

CH3iCOOK  CH3 

CH2!COOK  =       CH2  +2C02  +  2K 

CH2  .  COOC2H5  CH2 .  COOC2H5 

Hofer 2  afterwards  electrolysed  ketonic  acids  (pyruvic  and  levulinic) 
and  obtained  diketones. 

CH3.CO.COO;K  CH3.CO 

|    +  2C02  +  2K 
CH3.CO.COO;K  CH3.CO 

Walker 3  found  that  by  electrolysing  sodium  diethyl  malonate  two 
molecules  link  up  to  form  the  anhydride  of  tetraethylsuccinic  acid, 
and  Wohl  and  Schweitzer,4  who  submitted  the  sodium  salt  of  acetal 
uialonic  aldehyde  to  the  current,  obtained  the  acetal  of  adipic  aldehyde. 

yCH(OC2H5)2  CH2 .  CH(OC2H5)2 

2CH/  =      |  +2C02 

XCOOK  CH2 .  CH(OC2H  )2 


Group  2.     Condensation  ly  Addition. 

Additive  Reactions.  Benzene  under  certain  conditions  forms 
additive  compounds  with  unsaturated  hydrocarbons,  as  in  the  union 
of  styrene  with  benzene,  which  combine,  giving  diphenylethane, 

C6H5CH  :  CH2  +  C6H,  =  (C6H5)2CH  .  CH3 

or  in  that  of  benzene  with  cinnamic  acid,  which  in  presence  of  sul- 
phuric acid  yield  diphenylpropionic  acid, 

C6H5CH  :  CH  .  COOH  +  CGH6  =  (C6H6)2CH  .  CH2 .  COOH 

The  production  of  cyclic  structures  have  been  observed  in  the  case 
of  acetylene,  which  when  passed  over  finely  divided  iron  gives  small 

1  Z*t.f.  Elektrochemie,  1897,  4,  55;  Ber..  1895,  28,  2427. 

2  Ber.,  1900,  33,  650. 

8  Trans.  Chem.  Soc.,  1905,  87,  961. 
4  Ber.,  1906,  39,  890. 


202  CHAIN  AND  RING  FORMATION 

quantities  of  benzene ; l  of  bromoacetylene,  which  exposed  to  light 
undergoes  a  similar  change,  yielding  tribromobenzene  ;  and  of  methyl- 
and  dimethyl-acetylene,  which  in  presence  of  strong  sulphuric  acid 
condense,  forming  respectively  mesitylene  and  hexamethylbenzene. 
Dobner2  has  observed  that  vinylacrylic  acid  unites  with  itself,  form- 
ing a  ring  compound  of  the  formula 

CH2 .  CH=CH  .  CII .  COOII 

i  I 

CH2 .  CH^CH  .  CII .  COOH 

A  very  interesting  case  of  ring  formation  by  addition  is  recorded 
by  Perkin,3  in  which  dibromodiallyl-malonic  ester  on  treatment 
with  alcoholic  potash  is  converted  into  m-toluic  acid,  a  reaction 
which  probably  occurs  in  the  following  way  : 


(CH,=CBr.CH2)2C 


/CO .  OR          CH2=C^CH         /H 

\  -* 

MX) .  OR         CH9=C=CH        \COOH 


XCO< 


2 
Dibromodiallyl-malonic  ester.  Intermediate  product. 

CH3.C_jOH 

->    HC/~    ~^C.  COOII 
CIT~CH 

w-Toluic  acid. 

Michael's  Reaction.4  Michael  has  shown  that  the  sodium  com- 
pounds of  acetoacetic  ester  and  malonic  ester  are  capable  of  forming 
additive  compounds  with  unsaturated  compounds  of  the  general 
formula  :  R .  CH :  CH  X  or  R .  C  •  C  .  X,  in  which  R  is  a  positive  or 
negative  organic  radical,  and  X  a  strongly  negative  radical  such  as 
carbonyl,  cyanogen,  &c.  The  sodium  attaches  itself  to  the  carbon 
atom  linked  to  the  negative  group  and  the  negative  radical  to  the 
positive  carbon  group.  The  first  example  studied  by  Michael  was 
the  condensation  of  sodium  malonic  ester  (prepared  by  the  action  of 
metallic  sodium  or  dry  sodium  ethoxide  on  the  ester  dissolved  in 
ether)  on  cinnamic  ester.  The  union  takes  place  in  the  following  way  : 

C6H5CH  :  CH  .  COOC2H5  C6H5CH .  CHNa .  COOC2H5 

NaCH(COOC2H5)2  CH(COOC2H5)2 


1  Moissan  and  Morueu,  Compt.  rend.,  1896,  122,   1240;  see  also  Compt.  rend., 
1900,  130,  1319,  and  Ckem.  Centralbl,  1902, 1,  77. 

2  Ber.,  1902,  35,  2129. 

3  Trans.  Chem.  Soc.,  1907,  91,  816,  840,  848. 

4  Michael,  J.  prakt.  Chem.,  35,  351;  43,  395;  45,  55;  49,  20;  Auwers,  Ber., 
1891,  24,  317,  2887  ;  1893,  26,  364  ;  1895,  28,  263  ;  Ruhemann  and  CuuniiigUn, 
Trans.  Chem.  Soc.,  1898,  73,  1006. 


MICHAEL'S  REACTION  203 

Acids  liberate  the  tribasic  ester  which,  by  hydrolysis,  can  be  con- 
verted into  the  dibasic  /?-phenylglutaric  acid, 

C6H5  .  CH  .  CH2  .  COOC2H5  Q,H5  .  CH  .  CH2  .  COOH 

CH(COOC2H5)2  (JH2  .  COOH 

Fumaric,  maleic,  aconitic,  crotonic,  citraconic,  and  itaconic  esters, 
acetylene  dicarboxylic  and  phenylpropiolic  esters  and  benzylidene 
acetone,  &c.,  behave  in  the  same  way,  though  there  is  a  considerable 
difference  in  the  rate  of  formation.1 

The  sodium  compound  of  cyanacetic  ester  resembles  malonic  ester  2 
and  has  been  utilized  by  Perkin  3  for  the  synthesis  of  isocamphoronic 
acid.  Dimethylglutaconic  ester,  when  digested  with  an  alcoholic 
solution  of  sodium  cyanacetic  ester,  yields  : 

C2H5OOC  .  C(CH3)2  .  CH  .  CHNa  .  COOC2H5 
NC.CH.COOC2H5 

If  the  resulting  ester  is  then  hydrolysed,  isocamphoronic  acid  is 
obtained,  which  consequently  has  the  formula  : 

(CH3)2C—  CH—  CH2.  COOH 
HOOC    CH2.COOH 

Isocamphoronic  acid. 

The  same  condensation  process  has  also  been  applied  to  the 
synthesis  of  cyclic  compounds  by  Vorlander.4  Benzylidene  acetone 
combines  with  sodium  malonic  ester,  forming  phenyldihydroresorcylic 
ester,6 

cooc2H5  coocyr. 

,CR  .  COOC2H5  CH__CO 

CGH5  .  CH<  -H>  C6H,  .  HC<  >CH2  +  C2H5OH 


\CH,.CO.CH3. 

Intermediate  additive  Phenyldihydroresorcylic  ester. 

compound. 

In  the  same  way  mesityl  oxide  may  be  converted  into  diinethyl- 
diketocyclohexane, 

1  Au\\ers,  Ber.,  1895,  28,  1131  ;  Annalen,  189C,  292,  147. 

*  Muller,  Coiyipt.  rend.,  1892,  114,  1204;  Noyes,  Ber.,  1899,  32,  22S9. 

3  Proc.  Chem.  Soc.,  1900,  214. 

4  Ber.,  1894,  27,  2053;  Annalen,  1896,  294,253. 

5  In  both  these  reactions  the  compound  in  the  second  stage  undergoes  the 
acetoacetic  ester  condensation  (see  p.  220). 


204  CHAIN  AND   RING  FORMATION 

(CH3)2C  :  CH  .  CO  .  CH3  (CH3)2C— CH2  -CO 

+  ->  |  | 

IICNa(COOC2H5)2  C2H5OOC .  CH— CO— CH2 

(CH3)2C— CH2-CO 

->  I  I 

H2C— CO  — CH2 

and  Knoevenagel  has  prepared  isoacetophorone  in  the  same  fashion, 
using  sodium  acetoacetic  ester  in  place  of  sodium  malonic  ester. 
Knoevenagel *  also  found  that  diethylamine  could  replace  sodium  or 
sodium  ethoxide  in  effecting  condensations  of  this  character. 

Bnchner-Cnrtins  Reaction.  This  reaction  yields  in  the  first 
instance  pyrazole  derivatives,  which,  by  loss  of  nitrogen,  may  be 
converted  into  true  condensation  products.  A  simple  illustration  of 
the  reaction  is  furnished  by  the  union  of  an  aldehyde  with  diazo- 
methane,  forming  a  ketone  by  elimination  of  nitrogen,2 

/N 

R.CH:0  +  CH2<|| 
\N 

R  .  CH— Ov  R  .  CH  x  R  .  CO 

->  I  >N    ->         !      >0  +  N2    -*  | 

CH2— W  CH/  CH, 


Intermediate  products. 

A  more  interesting  application  of  the  method  is  the  preparation  of 
those  pyrazole  compounds  which  yield  cyclopropane  derivatives  by 
loss  of  nitrogen. 

It  is  well  known  that  acetylene  combines  directly  with  diazo- 
methane,  giving  pyrazole,3 

/ITT  r*TT  f^TT r*TJ 

v^Xl  ^-"-2  v/Xl V^±J.\ 

III     +   /\       =      I  >NH 

CH       N=N  CH^rN  / 

Acetylene  dicarboxylic  ester  combines  in  a  similar  way  with  diazo- 
methane,  the  resulting  product  being  pyrazole  dicarboxylic  ester. 
Now,  if  in  place  of  acetylene  or  its  dicarboxylic  ester,  esters  of  the 
define  acids  such  as  fumaric,  maleic,  and  aconitic  esters  be  substituted, 
pyrazole  compounds  are  formed  as  before,  but  readily  lose  nitrogen 
on  heating,  and  the  ring  closes  up  and  gives  a  cyclic  compound. 

Fumaric  ester  and  diazomethane  react,  giving  cyclopropane  dicarb- 
oxylic ester,  as  follows : 

1  Ber.,  1904,  37,  44G4.  2  Schlotterbeck,  Ber.,  1907,  40,  479. 

8  v.  Pechmann,  Ber.,  1898,  31,  2950. 


BUCHNER-CURTIUS  REACTION  205 

CH2    CH.COOC2H5  CH2— CH  .  COOC2H5 

N=N  +CH .  COOC2H-(  N        CH .  COOC,H5 

V 

CH2— CH .  COOC2H5 

^CH .  COOC2K5 

If,  in  place  of  diazomethane,  diazoacetic  ester  is  used,  a  cyclopro- 
pane tricarboxylic  ester  is  formed.1 

Addition  of  Hydrogen  Cyanide.  The  addition  of  hydrogen 
cyanide  to  aldehydes  and  ketones  giving  cyanhydrins  affords  an 
extremely  useful  method  for  the  preparation  of  hydroxy  acids  con- 
taining an  additional  carbon  atom  in  the  chain.  The  addition  of  this 
reagent  is  not  restricted  to  the  CO  group ;  for  it  is  found  that  in 
unsaturated  ketones  and  acids  containing  the  grouping  C :  C .  CO 
hydrogen  cyanide  will  attach  itself  by  preference  to  the  double  bond, 
thus  forming  ketonic  cyanides  and  ketonic  acids.2  Benzalmalonic 
ester  combines  as  follows  : 

/COOC2H5  /COOC2H5 

C6H5CH:C<  +HCN     =    CGH5CH.CH< 

NCOOOJI,  \cooc2H5 


Organo-metallic  Compounds.  The  extraordinary  development 
which  organic  synthesis  owes  to  the  use  of  organo-metallic  com- 
pounds has  its  origin  in  Frankland's  discovery  of  the  zinc  alkyl 
compounds.  The  preparation  of  these  compounds  need  not  be 
described.  They  are  extremely  unstable  liquids  which  are  charac- 
terised by  their  strong  affinity  for  either  free  or  combined  oxygen 
and  for  the  halogens.  It  is  on  these  properties  that  their  manifold 
transformations  depend.  Paraffins  may  be  derived  from  them  either 
by  the  direct  action  of  water,8  of  alkyl  iodides,  or  of  dihalogen  com- 
pounds.4 The  following  reactions  illustrate  each  of  the  methods  : 

Zn(CH3)2  +  2H20  =  2CH4  +  Zn(OH)2 
Zn(CH3)2  +  2(CH3)3CI  =  2(CH3)4C  +  ZnI2 
Zn(CH3)2  +  CH3  .  CC1S .  CH3  =  C(CH3)4  +  ZnCl2 

1  Buchner  and  Curtius,  Ber.,  1885,  18,  237. 

2  Lapworth,  Trans.  Cliem.  Soc.,  1903,  83,  995  ;  1904,  85,  1206,  1214  ;  1906,  80, 
945  ;  Brest  and  Kallen,  Annalen,  1896,  293,  338. 

3  Frankland,  Annalen,  1849,  71,  203  ;  1850,  74,  41. 

4  Friedel  and  Ladenburg,  Annalen,  1867, 142,  316 ;   Liwow,  Zeits.,  1871,  257.  - 


206  CHAIN  AND   SING   FOKMATION 

Zinc  Alkyl  Condensations  (Frankland's  Method).  The  dis- 
covery by  Frankland  and  Duppa  l  of  the  formation  of  a  hydroxy  acid 
from  zinc  ethyl  and  oxalic  ester  prepared  the  way  for  new  and 
unlooked-for  synthetic  uses  of  the  zinc  alkyl  compounds.  If  to  one 
molecule  of  ester  two  molecules  of  zinc  alkyl  are  added  and  the 
product  decomposed  by  water,  diethylglycollic  ester  is  obtained. 
The  following  equations  represent  the  course  of  the  reaction  : 

CH 


COOC2H5  | 

|  +  Zn(C2H5)2  =  C 

COOC2H5  |XOC2H5 

coocyi5 

C2H5  C2H- 

|   /OZnC2H.  |  /OZnC2H-  /OC2H5 

C<  +  Zn(C2H,)2  =  C<  +  Zn< 

IXOC2H5  |\C2H5  \C2H5 

COOC2H3  COOC2H5 


I  /OZnC2H3  .    | 

+  2H20  =  (HO)C  .  C.H,  +  Zn(OH)2  +  C2H 


c< 

I  XLH, 


COOC2H5  COOC2H5 

Diethylglycollic  ester. 

The  same  product  was  also  prepared  by  heating  a  mixture  of  oxalic 
ester,  alkyl  iodide,  and  zinc.2 


COOC2H5  (C2H,)2  .  CO  . 

|  +4Zn  +  4C2H5I=  +2ZnI2 

COOC2H5  COOC2H5 

-fZn 
(C2H5)2CO  .  ZnC2H5  (C2H5)2C(OH) 

|  +2H20=  |  +Zn(OH)2-fC.,Hc 

COOC2H5  COOC2H5 

This  was  followed  by  the  researches  of  Wagner,8  on  the  action  of 
zinc  alkyl  on  aldehydes,  which  led  to  the  synthesis  of  secondary 
alcohols  ;  of  Saytzeff,4  who  applied  a  similar  reaction  to  the  ketones 
and  obtained  tertiaiy  alcohols  ;  of  Butlerow,6  who  prepared  alcohols 
from  the  acid  chlorides  ;  of  Freund,6  who  obtained  ketones  from  the 


1  Annalen,  1863,  126,  109. 

2  Frankland  and  Duppa,  Annalen,  1863,  126,  109  ;  1868,  135,  26. 

8  Annalen,  1876,  181,  261.  *  Annalen,  1877,  185,  151. 

5  Annalen,  1867,  144,  1.  «  Annalen,  1861,  118,  3. 


ZINC  ALKYL   CONDENSATIONS  207 

acid  chlorides  ;  of  Wagner,  Saytzeff,  and  Kannonikoff,1  who  con- 
verted aliphatic  esters  into  secondary  and  tertiary  alcohols.  The 
following  examples  illustrate  the  different  types  of  reactions  referred 
to.  Aldehydes  and  zinc  alkyls  form  secondary  alcohols.  Acetalde- 
hyde  and  zinc  ethyl  yield  secondary  butyl  alcohol. 

H 

CH3CHO  +  Zn(C2H5)2  =  CH3  .  C—  OZnC2H5 


Cs 


H  H 

CII3 .  C— OZnC2H5  +  2H20  =  CH3  .  C— OH  +  Zn(OH)2  4  C  JI6 

\H5 

Secondary  butyl  alcohol. 

Formaldehyde  gives  primary  alcohols  by  a  similar  series  of  changes, 
whereas  ketones  yield  tertiary  alcohols. 

Formaldehyde  and  zinc  ethyl  yield  primary  propyl  alcohol,  whilst 
acetone  and  zinc  ethyl  give  tertiary  amyl  alcohol. 

HCHO  4-  Zn(C2H5)2  =  HCH  .  OZnC2H5 


HCH  .  OZnC2H6  +  2H2O  =  HCH(OH)  +  Zn(OH)o  +  C2H6 
I  I 

C2H5  C2H5 

Primary  propyl  alcohol. 

CH3  CH3  C2H- 

CO  +  Zn(C2H5)2  =      C 

I  /\ 

CH3  CH3  OZnC2H5  - 

CH3  C2H5  CH3  Cj,H5 

C  +2H20=       C          +Zn(OH)2  +  C2H6 

CH3OZnC2H5  CH3OH 

Tertiary  amyl  alcohol. 

Acid  chlorides  react  with  one  and  two  molecules  of  zinc  alkyl. 
Acetyl  chloride  and  zinc  ethyl  form  methylethyl  ketone. 

Ib75;  175,  351  j  1877,  185,  1*9,  148,  1C9. 


208  CHAIN  AND  RING   FORMATION 

<l  PI 

+  Zn(C2H5)2  =  CH3.C/ 
|   \OZnC2H5 

/Cl  X6H: 

CH3 .  C<  +  2H.O  =  CH3 .  C<  i       |  +  Zn(OH)Cl  +  C2H0 

|  xOZnC2H5 


Methylethyl  ketone. 

If  the  intermediate  product  is  allowed  to  react  with  a  second 
molecule  of  zinc  alkyl,  a  tertiary  alcohol  results. 


Cl 

CH, .  C/  +  Zn(C2H5)2  =  CH3 .  C<f  +  ZnCl(C2H5) 

|    X)ZnC2H5  |   \OZnC2H5 

C2H5  C2H5 

CH     C' 

\OZnC2H5  +  2H20  =  CH3 .  C(OH)  +  Zn(OH)2  +  C2H6 

Tertiary  hexyl  alcohol. 

With  the  esters  a  similar  process  occurs.  Methyl  formate  and  two 
molecules  of  zinc  ethyl  yield  a  secondary  butyl  alcohol.  The  reaction 
occurs  in  two  steps. 

/"V/^TT  /^/"^TT 

j\J\jtt.<>  s\J\jLl§ 

HC/  +Zn(C2H5)2  =  HC< 

V)  I  XOZnC2H5 

/OCH3  /C2H5  xOCH3 

HC<  +  Zn(C2H5)2  =  HC<  +  Zn< 

\OZnC2H5  |   \OZnC2H5          XC2H5 


ft          if  A          V 

HC— OZnC2H5  +  2H20  =  HC  .  OH  +  Zn(OH)2  +  C2H6 

\H  in 

^2115  Ugllf 

Diethylcarbinol. 

Other  fatty  esters  like  acetic  ester  will  naturally  yield  tertiary 
alcohols  by  this  process. 

Magnesium  Alkyl  Condensations  (Grignard's  Reaction).  The 
use  of  magnesium  in  place  of  zinc  for  introducing  radicals  into 
organic  compounds  in  the  manner  employed  by  Frankland  and  Duppa 


MAGNESIUM  ALKYL  CONDENSATIONS  209 

was  first  suggested  in  1899  by  Barbier,1  who  converted  methyl- 
heptenone  into  a  tertiary  alcohol  by  the  action  of  methyl  iodide  in 
presence  of  magnesium.  In  the  following  year  the  study  of  the 
preparation  and  synthetic  uses  of  magnesium  alkyl  compounds  was 
taken  up  by  Grignard,  who  published  an  account  of  his  results  in  the 
Comptes  rendus.2  Since  then  the  reaction  has  been  applied  by  himself 
and  his  collaborators,  as  well  as  by  a  host  of  other  workers,  in  so 
many  directions  that  it  will  be  impossible  to  do  more  than  indicate 
the  nature  of  the  main  applications  of  this  interesting  and  useful 
synthetic  process.  For  a  more  complete  account  the  references  given 
in  the  footnote  may  be  consulted.3 

Although  the  behaviour  of  the  magnesium  alkyl  compounds  will 
be  seen  to  resemble  in  many  respects  that  of  the  zinc  alkyls,  their 
greater  reactivity,  owing  no  doubt  to  the  more  electropositive 
character  of  the  metal,  as  well  as  the  convenience  of  their  prepara- 
tion, offer  great  advantages  over  the  use  of  the  zinc  compounds. 
Moreover,  aromatic  halogen  compounds,  such  as  bromo-  and  iodo- 
benzene  and  toluene,  may  be  used  in  addition  to  the  alkyl  halides. 

The  method  of  preparation  consists  in  adding  to  one  atomic  pro- 
portion of  clean  metallic  magnesium  wire,  ribbon,  or  filings, 
suspended  in  perfectly  dry  ether,  a  molecular  equivalent  of  the  alkyl 
iodide  or  bromide  (or  phenyl  or  tolyl  bromide),  also  dissolved  in  ether. 
The  magnesium  dissolves  with  evolution  of  heat,  and  a  solution  is 
usually  obtained  which  contains  the  magnesium  alkyl  or  aryl 
bromide  or  iodide.  If  methyl  iodide  is  used,  and,  after  the  action 
is  complete,  the  excess  of  ether  is  evaporated  and  the  product  heated 
to,  100-120°  in  a  vacuum  to  remove  the  last  traces  of  solvent,  the 
composition  of  the  residue  is  found  to  correspond  to  a  substance  of 
the  formulae  : 

MgCH3I.(C2H6)20 

The  ether  was  regarded  by  Grignard  as  ether  of  crystallization, 
but  Baeyer  and  Villiger  regarded  it  as  part  of  a  compound  containing 
quadrivalent  oxygen  (I).  Grignard  afterwards  adopted  the  view,  but 
distributed  the  magnesium  alkyl  halide  differently  (II)  *\ 

C2H5X      /MgCHg  C2H5X       Mgl 


0 
\C 


C2H         M  C,H         \CH3 

I.  II. 

There  are  reasons  for  supposing  that  the  ether  plays  an  essential 

1  Compt.  rend.,  1899,  128,  110.  a  Compt.  rend.,  1900,  130,  1322. 

3  J.  Schmidt,  Ahrens'  Vortrage,  1905,  10,  68;  A.  McKenzie,  Brit.  Ass.  Reports* 
1907,  p.  273;  Amer.  Chem.  Journ.,  1905,  33,  318. 

TT.  I  p 


210  CHAIN  AND  RING  FORMATION 

part  in  the  synthetic  process  to  which  the  magnesium  compound  is 
applied,  but  discussion  of  the  mechanism  of  the  reaction  is  reserved 
until  some  of  its  more  important  applications  have  been  considered. 
Hydrocarbons.  The  magnesium  alkyl  or  aryl  iodide  is  decomposed 
by  water  or  alcohol,  or  indeed  by  any  compound  which  contains 
a  hydroxyl  group,  giving  a  hydrocarbon. 

RMgl  -f  H20  =  R  .  H  +  Mgl(OH) 
RMgl  +  C2H6OH  =  R  .  H  +  MfeI(OC2H5) 

The  method  has  been  applied  to  the  estimation  of  hydroxyl  groups 
in  organic  compounds.1  Ammonia  and  primary  amines  react  in  the 
same  way  by  giving  up  hydrogen  to  the  radical  and  entering  into 
union  with  the  magnesium  halide. 

RMgl  +  RWH,  =  R  .  H  +  IPNHMgl 

A  methyl  group  may  be  introduced  into  an  aromatic  hydrocarbon 
by  employing  the  aryl  magnesium  bromide  in  conjunction  with 
methyl  sulphate  (Werner  and  Zilkens). 


CH3  .  C6H4MgBr  +  (CH3s04  =  C0H4(CH  J2  +  CH3  .  S04MgBr 

Alcohols  may  be  obtained  from  aldehydes,  ketones,  acid  chlorides. 
esters,  &c.,  by  methods  which  offer  a  close  analogy  to  the  zinc  alkyl 
jreactions. 

H 

R.CHO-fR^gBr    -*    RC-OMgBr+H2O    -*    R.CHfOHJ-R1 

R1 

Aldehyde.  Secondary  alcohol. 

Primary  alcohols  can  be  obtained  from  formaldehyde,  or  more 
conveniently  from  its  polymeric  form,  trioxymethylenet  They  have 
also  been  prepared  from  ethylene  oxide  and  ethylene  chlorhydrin 
(Blaise).  In  the  first  case  the  action  takes  place  by  cleavage  of  the 
ring  : 

CH2X  /R 

>0  +  Mg<        =  R  .  CH2  .  CH2OMgBr  ->  R  .  CH2CH  ,011 
CH/  \Br 

In  the  second  case  it  occurs  in  two  phases,  vthe  hydroxyl  group  being 
first  attacked  and  then  the  halogen,  on  addition  of  a  second  molecule 
of  reagent. 

1  Hibbert  and  Sudborough,  Tram.  Chern.  Soc.,  1904,  85,  933  ;  Zerewitiiioff,  Ber., 
1907,  40,  2023. 


MAGNESIUM  ALKYL  CONDENSATIONS  211 

RMgBr  +  CH2C1  .  CH2OH  =  EH  +  CH2C1  .  CH2OMgBr 
R*MgBr  +  CH2C1  .  CH2OMgBr  =  R'CH,  .  CH2  .  OMgBr 

Tertiary  alcohols  are  readily  prepared  from  ketones,  esters,  and 
acid  chlorides. 

T>  T>  T> 

\CO  +  R*MgBr    ->     R  .  C^OMgBr    ->     R  .  C/(OH) 
B/  \R  \Rl 

The  process  may  be  applied  to  cyclic  ketones,  ketonic  acids,  di- 
ketones,  and  quinones.  In  the  last  two  cases  the  reaction  may  be 
regulated  so  that  either  one  or  both  ketone  groups  are  involved.  It 
is  an  interesting  fact  that  a  tautomeric  ketonic  ester,  such  as  aceto- 
acetic  ester,  reacts  in  the  enol  form,  that  is,  forms  an  additive 
compound  with  the  reagent,  which  is  decomposed  by  water  and  the 
ester  regenerated.  If  alkyl  groups  are  introduced,  the  ester  then 
behaves  as  a  ketone.  This  reaction  has  been  applied  to  the  formation 
of  cyclic  compounds  by  Zelinsky  and  Moser1  in  the  following 
ingenious  way,  from  to-acetobutyl  iodide. 

C1I3.CO    I  CH3.CO  Mgf  CH3C.OMgI 

HoC/        NcH     -*   HC,/ 


CH2  H2C—         -CIL  H2C 


CH3.C(OH) 


.i  4 

Esters  react  as  follows : 

<O  /OMgBr 

-f  R  MgBr  =  R .  C\— OC.^U- 
f\r*  TI  \T?I 

UL2±15  ^K1 

/OMgBr  /OMgBr 

B .  C^OC2H5  +  B*MgBr  =  R .  C^-R2         +  MgBr .  OC2H5 

/OMgBr  /R2 

B .  C^R2         +  H20  =  R .  C(f(OH)  +  MgBr .  OH 

\RI  \RX 

In  the  case  of  dibasic  esters,  both  ester  groups  will  react,  forming 
glycols.  If  formic  ester  is  used,  a  secondary  alcohol  results. 

Acid  chlorides  react,  as  in  the  case  of  the  zinc  alkyl  compounds,  in 
two  phases,  giving  ketones  in  the  first  and  tertiary  alcohols  in  the 
second.  Carbonyl  chloride  behaves  in  a  similar  fashion : 

1  Ber.j  1902,  35,  2684. 

p  2 


212  CHAIN  AND   RING  FORMATION 

COCl2  +  3RMgBr  =  CR3OMgBr  +  MgCl2  +  MgBr2 
CRaOMgBr+H20  =  R3C(OH)  -f  Mg(OH)Br 

Anhydrides  and  lactones  also  give  tertiary  alcohols. 

It  frequently  happens  that,  in  the  reactions  with  aldehydes  and 
ketones,  an  unsaturated  hydrocarbon  appears  in  place  of  the  alcohol. 
This  must  be  ascribed  to  a  secondary  process  (whereby  water  is 
eliminated),  which  it  is  often  possible  to  promote  or  prevent  by 
modifying  the  conditions.  Acetophenone,  for  example,  may  be 
made  to  yield  the  unsaturated  hydrocarbon  in  place  of  the  alcohol  by 
raising  the  temperature  at  the  end  of  the  process. 

Ct$H6v 

>C:CHo 
CH/ 

a-Met  b  y  Isty  re  ne  . 

Aldehydes.  Quite  a  number  of  methods  have  been  elaborated  for 
producing  aldehydes,  of  which  the  following  are  the  most  important. 
By  the  use  of  dimethylformamide  the  following  changes  occur 
(Bouveault)  : 

HCO.NRRi  +  R^gl    ->    HCR^OMglJNRR1  +  H2O 

->    R2CHO  +  NHRR1  +  Mg(OH)I 

Under  ordinary  conditions  the  effect  of  the  Grignard  reagent  on 
formic  ester  is  to  give  a  secondary  alcohol,  but  Gattermann  found  that 
by  using  three  molecules  of  ester  and  keeping  the  temperature  low, 
the  aldehyde  is  formed  (Gattermann). 

HCO  .  OC2H5  +  RMgBr  =  RCHO  +  MgBrOC2Hfi 
Orthoformic  ester  may  also  be  used  (Boudroux). 

CH(OC2H6)3  +  RMgBr  =  RCH(OC2H5)2  +  MgBrOC2H5 

RCH(OC2H5)2  +  H20  =  RCHO  +  2C2H5OH 

Gattermann  introduced  ethoxymethylene  aniline  in  place  of  ethyl 
formate,  the  reaction  taking  place  as  follows  : 

C6H5N  :  CH  .  OC2H5  +  RMgBr  =  C6H5N  :  CHR  +  C2H5OMgBr 

C6H5N  :  CHR  +  H20  =  R  .  CHO  +  CGH5NH2 

Another  method  which  also  yields  aldehydes  is  that  of  Sachs  and 
Loevy  in  which  isocyanides  are  used. 


=  RN  :  C 

tfgBr 
M 
RN  :  C<;  +  H2O  =  RN  :  CHR1  +  MgBr(OH) 

XMgBr 
RN  :  CHR1  +  H20  =  RNH2  +  CHO  .  R1 


MAGNESIUM  ALKYL  CONDENSATIONS  213 

Ketones  can  be  prepared  from  cyanogen,  cyanides,  and  amides. 

(CN),  +  RMgI  -NC.€f 

\R 


x  x» 

NC  .  C<  +  RMgl  =  RCf  +  Mg(CN)I 

\R  \R 

,NMgI 
R  .  C<;  +  2H,0  =  R  .  CO  .  R  +  Mgl(OH)  +  NH3 


In  the  same  way, 

x 
RCN  +  R'MgBr    -»     RC<  +  2H..O 

R1 
=  R  .  CO.  R1  +  Mg(OH)Br  +  NH3 

Ketonic  esters  may  be  obtained  by  the  same  process  from  cyanogen 
esters.  Cyanacetic  ester,  for  example,  with  magnesium  methyl  iodide 
yields  acetoacetic  ester  (BJaise). 

The  action  upon  amides  is  represented  as  follows  : 


y 

R  .  CONH2  +  2MgR^  =  R  .  C^-NHMgl  +  R1!!  - 

\R! 

R  .  C(OMgI)(NHMgI)Rl  +  2H2O  =  R  .  C(OH)(Ntt.2)Rl 
+  MgI2  +  Mg(OH)2 

The  last  product  loses  ammonia  and  gives  the  ketone. 

Acids  and  Esters.  Acids  are  obtained  by  passing  carbon  dioxide 
into  the  ethereal  solution  of  the  magnesium  alkyl  compound  and 
decomposing  the  product  with  water  or  sulphuric  acid,  or,  if  the 
sodium  salt  is  required,  with  sodium  hydroxide  solution  (Grignard). 

X)MgBr  H20 


RMgBr  +  CO.,    ->     R.C<  ->      R.<X        +  MgBr(OH) 

X) 


If  the  intermediate  compound  is  further  acted  upon  by  two  mole- 
cules of  magnesium  alkyl  halide,  and  the  product  decomposed  with 
water,  a  tertiary  alcohol  is  formed. 

R  .  CO  .  OMgBr  +  2R1MgBr  =  CRR^1  .  OMgBr  +  (MgBr)2O 
H2O 


By  using  chloroformic  ester  with  the  Grignard  reagent,  esters  are 
obtained  (Houben). 

R  .  MgBr  +  Cl  .  COOC2H5  =  R  .  COOC2H5  +  MgClBr 


214  CHAIN  AND   RING  FORMATION 

The  reaction  may  proceed  to  a  second  phase,  yielding  a  tertiary 
.alcohol,  as  already  explained  (p.  211). 

Carbonic  esters  may  also  be  used  in  the  preparation  of  esters 
(Tschitschibabin). 

RMgBr  +  CO(OC2H5)2  =  RC(OMgBr)(OC2H,)2 
RC(OMgBr)(OC2H5),  +  H20  =  R  .  COOC2H-  +  C2H5OH  +  MgBr(OH) 

Ortho-carbonic  ester  reacts  in  a  similar  manner. 

RMgBr  +  C(OC2H5)4  =  R  .  C(OC2H5)3  +  MgBr(OC2H5) 
RMgBr  +  R  .  C(OC2H5)3  =  R2C(OC2H5)2  +  MgBr(OC2H5) 

In  this  case  an  acetal  is  formed. 

Sulphur  Acids.  Sulphur  dioxide  reacts  like  carbon  dioxide  and 
forms  sulphinic  acids  (Rosenheim  and  Singer). 

H.O 
RMgBr  +SO2    -»     R.S02MgBr    -»     R  .  S02H  +  MgBr(OH) 

The  same  product  is  obtained  from  sulphuryl  chloride  (Oddo). 
RMgBr  +  S02C12  =  R  .  S02C1  +  MgClBr 
R  .  SOoCl  +  RMgBr  =  R  .  S02MgBr  +  RC1 
R  .  S02MgBr  +  H20  =  R  .  S02H  +  MgBr(OH) 

Carbithionic  acids  are  formed  by  the  action  of  carbon  bisulphide  on 
the  reagent  in  the  same  way  as  the  carboxylic  acids  by  the  use  of 
carbon  dioxide  (Houben). 

Amides  of  the  aromatic  series  may  be  obtained  from  aryl  carb- 
imides  (Blaise). 

/OMgl     H2o 

C6H5NCO  +  IMgR    -»     CCH5NC<  -^     CCH5NHCOR 


+  Mgl(OH) 

Similar  products  are  obtained  by  forming  the  magnesium  compound 
of  a  primary  aromatic  amine,  RNHMgl,  and  acting  upon  it  with  the 
ester  of  a  monobasic  acid  (Bodroux). 

2RNHMgI  +  R'COOR2  =  MgI(OR12)  +  R1  .  C(NHR)2OMgI 
R1  .  C(NHR)2  .  OMgl  +  HC1  =  RNH2  +  R^ONHR  +  MglCl 

If,  in  place  of  a  monobasic  ester,  ethyl  carbonate  is  substituted,  a 
ure  thane  is  formed  (Bodroux). 

2RNHMgI  +  CO(OC2H5)2  =  (RNH)2C(OC2H5)  .  OMgl  +  Mgl  .  OC2H5 
(RNH)2C(OC2H5)  .  OMgl  +  H2O 

-  RNH  .  COOC2H5  +  RNH2  +  Mgl(OH) 


MAGNESIUM  ALKYL  CONDENSATIONS  215 

Thioanilides  are  obtained  by  substituting  mustard  oils  for  the  car- 
bimides  in  the  above  reaction  (Sachs  and  Loevy). 

Hydroxylamitie  Derivatives.  Both  nitric  oxide  and  nitrogen  peroxide 
react  with  the  Grignard  reagent,  the  former  giving  nitroso  hydro- 
xylamines  and  the  latter  dialkyl  hydroxylamines  (Wieland). 

/OMgBr  /OH 

ON.N<  -*    ON.N< 

\R  XR 

The  mechanism  of  the  second  reaction  has  not  been  explained,  but 
is  no  doubt  due  to  partial  reduction  of  the  peroxide  by  the  reagent. 
Hydroxylamine  derivatives  may  also  be  obtained  from  amyl  nitrite  as 
follows  : 

ON  .  OC5Hn  +  2MgIR  =  NRR  .  OMgl  +  C5HnOMgI 
NRR .  OMgl  +  H20  =  N(R)2OH  +  Mgl(OH) 

Diazoamino-compounds.  Aliphatic  as  well  as  aromatic  diazoamino- 
compounds  can  be  prepared  from  alkyl  and  aryl  azides.1 

MgBr 

RN/ll  +  R^gBr  =RN.N:NRi    -»    RNH .  N :  N .  R^  +  MgBr(OH) 
\N 

Additive  Compounds.  Kohler2  has  made  a  careful  study  of  the 
action  of  the  Grignard  reagent  on  the  unsaturated  aldehydes  and 
ketones  containing  the  group  C  :  C  .  CR  :  0.  Several  reactions  are 
possible.  Addition  may  occur  at  the  double  bond  or  with  the  ketone 
or  aldehyde  group,  or  again,  following  Thiele's  rule  (p.  133),  in  the  1 .  4 
position.  All  these  effects  have  been  observed  and  are  found  to 
depend  upon  the  nature  of  the  attached  radicals  and  may  be  summa- 
rized as  follows  : 

1.  In  aldehydes  and  ketones  in  which  R  is  hydrogen  or  an  alkyl 
group,  a  normal  reaction  with  the  CO  group  takes  place,  with  the 
formation  of  a  tertiary  alcohol. 

•  2.  If  the  attached  radical  is  aromatic,  addition  occurs  in  position 
1  .  4,  and  a  ketone  is  formed,  as  in  the  case  of  cinnamylphenyl 
ketone. 

C6H5CH  :  CH .  CO  .  C6H5  +  C6H5MgBr 

=  CCH5CH(C6H5).  CH  :  C(OMgBr)C(iH5 

-*    C6H5CH(C0H5) .  CH2 .  CO .  C6H6 

1  Dimroth,  Ber.,  1906,  39,  3905. 

2  Amer.  Chan.  Journ.,  1905,  33,  153,  333  ;  34,  132. 


216  CHAIN  AND  RING  FORMATION 

3.  If  the  attached  radical  is  an  alkyl-oxy  group,  that  is,  if  the 
compound  is  an  unsaturated  ester,  addition  either  takes  place  as  in 
(2)  or  the  alkyl-oxy  group  is  replaced  by  the  radical  of  the  reagent. 
The  former  occurs  with  an  aryl  magnesium  halide,  and  the  latter 
with  an  alkyl  compound. 

For  example,  phenylcinnamic  ester  reacts  as  follows  with  phenyl 
magnesium  bromide  : 

CGH5CH  :  C(CCH,)  .  COOC2H5  +  MgBrCflH3 

->    CCH,CH  .  C(CCII5)  :  CO  .  OR 

CGH5  MgBr 

C6H5CH(C6H5)  .  C(CGH6)  :  COR(OMgBr)  +  HC1 

=  (C6H5)2CH  .  CH(C6H5)  .  COOR  +  MgBrCl 

Additive  compounds  are  also  formed  with  unsaturated  nitrogen 
compounds  such  as  benzylidene  aniline, 

CGH5N  :  CH  .€GH5  +  MgCH3I  =  CGH5N(Mgl)  .  CH(CH3)  .  C6H5 


which  yields  the  secondary  amine  on  decomposition  with  water 
(Busch).  Oximes  behave  similarly,  the  radical  attaching  itself  to  the 
unsaturated  carbon  and  the  magnesium  halide  to  the  nitrogen. 
Triazo-compounds  also  react  by  cleavage  of  the  nitrogen  ring,  followed 
by  the  formation  of  diazoamino-compounds  (Dimroth). 

/N 

RN<   11  +  IPMgl  =  RN(MgI)N  :  NR1 
\N 

RN(MgI)N  :  Nil1  +  H20  =  RNH  .  N  :  NR1  +  Mgl(OH) 

The  reaction  may  be  applied  indifferently  to  the  preparation  of  both 
aliphatic  and  aromatic  compounds. 

This  does  not  exhaust  the  many  changes  which  may  be  rung  on  the 
reaction,  but  the  above  examples  will  serve  to  illustrate  the  general 
character  of  the  process.  It  will  be  seen  that,  apart  from  the  simplicity 
and  convenience  of  the  method,  the  magnesium  compounds  are  much 
more  reactive  than  the  zinc  alkyls,  and  their  combination  may  be 
effected  with  nitrogen  much  in  the  same  way  as  with  oxygen,  thereby 
increasing  the  range  of  their  application.  It  should  be  observed  that 
the  metal  always  attaches  itself  to  the  more  electronegative  element 
(0  and  N),  either  by  adding  itself  to  the  latter  if  unsaturated,  or  by 
replacing  the  hydrogen  when  combined  as  hydroxyl  or  amino  groups. 


MAGNESIUM  ALKYL  CONDENSATIONS  217 

It  has  been  suggested  by  Tschelinzeff  l  that  the  ether  which  appeai-s 
to  form  a  compound  with  the  magnesium  alkyl  halide  acts  catalyti- 
c-ally at  low  temperatures,  for  although  interaction  between  the  magne- 
sium and  alkyl  halide  takes  place  in  benzene  or  xylene,  it  is  necessary 
to  boil  the  liquid,  whereas  the  presence  of  a  little  ethyl  or  amyl  ether 
or  anisole  (methylphenyl  ether)  causes  combination  at  the  ordinary 
temperature.  He  considers  the  effect  of  the  ether  is  to  dissociate  the 
alkyl  halide  by  forming  the  oxonium  compound,  thus  assisting  union 
with  the  metal  : 


-+ 
C.2H/     \X  C2H  X 

Tertiary  amines  such  as  dimethylaniline  may  replace  ether  as  the 
catalyst,  and  their  reaction  is  explained  in  a  similar  way  by  the 
disruption  of  the  alkyl  halide  RJX  from  the  quinquevalent  compound. 

R1 

(R)3N/ 
\X 

A  further  examination  of  the  ether  compounds  of  the  alkyl  magne- 
sium halide  has  shown  that  the  latter  unites  with  two  molecules  of 
ether,  corresponding  thus  to  Zelinsky's  compound  with  magnesium 
iodide  MgI2  .  2(C.2H5)20.  The  evidence  for  this  was  given  by 
Tschelinzeff,  who  showed  that  on  adding  ether  to  a  benzene  solution 
of  magnesium  alkyl  iodide,  equal  quantities  of  heat  are  evolved  for 
each  of  the  first  two  molecular  proportions  of  ether  added. 

Reformatsky's  Reaction.  A  reaction  which  may  be  regarded  as 
a  modification  of  Frankland's  and  Grignard's  was  first  suggested  by 
Fittig  and  Daimler.2  They  attempted  to  combine  chloracetic  ester 
with  oxalic  ester  in  presence  of  zinc,  in  the  expectation  of  obtaining 
a  product  similar  to  that  of  Frankland,  in  which  the  acetic  ester  group 
would  play  the  part  of  an  alkyl  radical.  The  reaction,  however,  gave 
instead  ketipic  (keto-adipic)  ester. 

CO.CH2.COOC2H5 
CO  .  CH2  .  COOC2H5 

Ketipic  ester. 

Reformatsky8  was  afterwards  more  successful,  and  obtained  a 
y3-hydroxy-isovaleric  ester  from  acetone,  iodoacetic  ester  and  zinc. 

1  B*r.,  1904,  37,  2084.  2  Bar.,  1887,  20,  202. 

8  Ber.,  1887,  20,  1210;  1895,  28,  2403,  2838. 


218  CHAIN   AND  RING  FORMATION 

CH3  CH3    OZnl 

\  V 

CO  +  CH2I .  COOR  +  Zn  -»  C  +  II2O 

CH3  CH3   CH2.COOR 

CH3 

^     C(OH) .  CH2 .  COOR  +  Znl(OH) 

CH3 

Lapworth  has  shown  that  the  ester  group  behaves  in  the  manner 
of  a  ketone  group,  and  has  succeeded  in  condensing  oxalic  ester  with 
bromacetic  ester,  and  also  two  molecules  of  bromacetic  ester  with 
zinc  or  magnesium,  with  the  object  of  throwing  light  on  the  aceto- 
acetic  ester  synthesis,  to  be  presently  discussed. 

C2H6OOC  .  COOC2H5  +  BrCH2 .  COOC2H5  +  Zn 

/OZnBr 


BrCH9.C-CH.COOC2H5   ->  BrCH2 .  CO .  CH2 .  COOC,H. 


=  C2H5OOC.  C^CH,.  COOR 
\OC2H5 

H20 

->    C2H5OOC .  CO  .  CH2 .  COOCJI.5 

Oxaloacetic  ester. 
BrCH2  .  COOC2H5  +  BrCH2 .  COOC2H5  +  Zn 

'OZnBr  H20 

r*tr     c 
,.    OW2.L 

NOC.'H, 

Bromacetoacetic  ester. 

The  reaction  has  since  been  used  for  the  synthesis  of  citric  acid  by 
Lawrence,1  dZ-camphoronic  acid  by  Perkin 2  and  by  others  for  similar 
condensations  (see  Part  III,  p.  235). 

In  the  first  case,  union  is  effected  between  bromacetic  ester  and 
oxaloacetic  ester,  and  proceeds  as  follows  : 

CH2Br          CO.COOC2H5 
I  +1  -fZn 

COOC2H5     CH2 .  COOC2H5 

C2H5OOC .  CH2 .  C(OZnBr) .  COOC2H, 

CH2 .  COOC2H5 
-  C2H5OOC .  CH2 .  C(OH) .  COOC2H5  +  Zn(OH)Br 

CH2.COOC2H5 

Citric  ester. 
1  Trans.  Chem.  Soc.,  1807,  71,  457.  2  Trans.  Chem.  Soc.,  1897,  71,  1173. 


REFORM ATSKY'S  REACTION  219 

In  the  second  synthesis,  a-bromoisobutyric  ester  and  acetoacetic 
ester  or  bromacetic  ester  and  dimethylacetoacetic  ester  in  presence  of 
zinc  were  first  combined,  giving  hydroxytrimethylglutaric  ester. 

(CH3)2 .  C-C(OH)-CH2 

I       I  I 

C2H5OOC    CH3        COOC2H5 

The  compound  was  then  acted  on  with  phosphorus  pentachloride 
and  converted  into  chlorotrimethylglutaric  ester.  On  boiling  with 
alcoholic  potassium  cyanide,  cyanotrimethylglutaric  ester  is  formed, 
and,  finally,  on  hydrolysing  with  hydrochloric  acid,  d?-camphoronic 
acid. 

(CH3)2C-CC1— CH9  (CH3),,C-C(CN) .  CH2 

III  ->  I      I  J 

C2H5OOC    CH3    COOC2H.5  C2H5OOC    CH3      COOC2H3 

Chlorotrimethylglutaric  ester.  Cyanotrimethylglutaric  ester. 

(CH3)2C-C(CH3)-CH2 

-*  "I  I 

HOOC    COOH    COOH 

<?Z-Camphoronic  acid. 

Magnesium  has  been  used  in  place  of  zinc  in  the  above  reaction.1 

Wallach  2  has  utilised  the  reaction  for  introducing  unsaturated  side- 
chains  into  cyclic  ketones.  Sabinaketone  can  be  converted  into 
sabinene  in  the  following  way  : 

OH      CH2 .  COOC.H5 


CO  C 

HC/\CH,  I 

\  "  +  CH.,Br .  COOC2H5  -> 

H2c\\/cH2        +  Zn        H2°  A/'011* 

C  +  H2°  C 

CH  CH 


Sabinaketone. 

The   latter,  when    heated    with   acetic    anhydride,    loses  carbon 
dioxide  and  alcohol  and  gives  : 

1  Zelinsky  and  Gutt,  J&r.,  1902,  35,  2140. 

2  Annakn,  1908,  360,  26 ;   1909,  365,  255. 


220  CHAIN  AND   RING   FORMATION 

CH, 


An  example  of  ring  formation  is  recorded  by  Reformatsky,1  who 
obtained  trimesic  ester  by  condensing  formic  ester  with  chloracetic 
ester  and  zinc. 

3C2H5OCH(OZnCl)CH2 .  COOC2H5  =  3C2H5OH  +  3Zn(OH)Cl 

HC C.COOC2H5 

+  C2H6OOC.C^        yCR 

HCT^ .  COOC2H5 

The  Acetoacetic  Ester  Condensation  (Union  of—  COOC2H^  + 
CH2 .  COOC2H5).  The  discovery  of  acetoacetic  ester  carries  us  back  to 
the  year  1863,  when  Geuther,2  who  held  the  view  that  acetic  acid 
contains  two  hydrogen  atoms  replaceable  by  metals,  sought  to  replace 
the  second  hydrogen  atom  in  ethyl  acetate  (since  it  could  not  be 
effected  with  sodium  acetate)  by  means  of  metallic  sodium.  - 

He  observed  the  evolution  of  hydrogen,3  the  formation  of  sodium 
ethoxide,  and  the  production  of  a  crystalline  sodium  compound  of  the 
formula  C^HgNaOg.  From  the  sodium  compound,  by  the  addition  of 
an  acid,  a  liquid  was  isolated  which,  though  neutral  to  litmus,  formed 
salts  with  metallic  bases.  He  found,  moreover,  that  the  sodium  of 
the  sodium  compound  reacts  with  alkyl  iodides  and  forms  a  series  of 
alkyl  ethers.  These  facts  led  Geuther  to  name  the  new  compound 
ethyldiacetic  acid,  and  to  represent  it  by  the  formula  : 

CH3.C(OH):CH.COOC2H5 

1  J.  russ.  phys.  chem.  Ges.,  1898,  30,  280.  2  Jahresb.,  1863,  323. 

8  It  was  subsequently  found  that  when  ethyl  acetate  is  pure,  little,  if  any, 
hydrogen  is  evolved,  but  according  to  Oppenheim  and  Precht  (Ber.,  1877,  9,  320) 
it  is  used  in  conjunction  with  sodium  to  convert  some  of  the  acetic  ester  into 
sodium  ethoxide. 

CH3.CO     Na  +  Ha     CH3.CH2.ONa 

I     +  + 

CH3 .  CH2 .  O       Na  CH3 .  CHa .  ONa 


THE  ACETO ACETIC   ESTER  CONDENSATION         221 
The  formation  of  the  sodium  salt  was  represented  by  the  equation  : 
2C2H3O .  C2H5O  +  Na2  =  H2  +  C2H5ONa  +  C6H9Na03 

Whilst  this  research  was  in  progress  Frankland  and  Duppa  were 
studying  the  action  of  alkyl  iodides  on  oxalic  ester  in  presence  of  zinc. 
In  extending  their  investigations  to  ethyl  acetate,  the  zinc  was 
replaced  by  the  more  energetic  metal,  sodium,  and,  during  the  solu- 
tion of  the  metal  in  the  ester,  the  evolution  of  hydrogen  was  observed. 
Without  isolating  the  product  they  proceeded  to  heat  up  the  solid 
mass  with  ethyl  iodide.  In  this  way  various  products  were  ob- 
tained and  separated  by  fractional  distillation.  Among  them  four 
compounds  boiling  between  120°  and  265°  were  isolated  and  charac- 
terized as  follows  :  (1)  butyric  ester,  (2)  diethylacetic  ester,  (3)  a  compound 
identical  with  the  ethyl  ester  of  Geuther's  ethyldiacetic  acid, 
which,  since  it  decomposed  with  alkalis  into  ethyl  acetone,  alcohol, 
and  carbon  dioxide,  was  termed  etliacctone  carbonate  of  ethyl,  and  (4)  a 
final  fraction  which  decomposed  in  the  same  manner  into  diethyl 
acetone,  alcohol,  and  carbon  dioxide,  and  received  the  name  of  dieth- 
aceione  carbonate  of  ethyl.  Frankland  and  Duppa  explained  the 
formation  of  the  first  two  compounds  by  supposing  that  ethyl  acetate 
is  converted  by  sodium  into  a  mono-  and  di-sodium  ethyl  acetate, 

CH2Na .  COOC2H5  and  CHNa2 .  COOC2H5 

which  with  ethyl  iodide  yield  ethyl-  and  diethyl-acetic  ester.  The 
formation  of  ethacetone  and  diethacetone  carbonate  of  ethyl  was 
explained  by  the  union  of  a  molecule  of  ethyl  acetate  with  a  molecule 
of  mono-  or  di-sodium  acetic  ester  formed  by  the  action  of  sodium  on 
acetic  ester. 

CH3 .  COOC2H5  +  CH2Na .  COOC2H5 

=  CH3 .  CO .  CHNa .  COOC2H5  +  C2H5OH 

CH3 .  COOC2H5  +  CHNa2 .  COOC2H5 

=  CH3 .  CO .  CNa2 .  COOC2H5  +  C2H5OH 

The  action  of  ethyl  iodide  on  the  two  sodium  compounds  would 
produce  ethacetone  and  diethacetone  carbonic  esters.  These  views 
were  generally  accepted,  and  the  name  of  Geuther's  ethyldiacetic  acid 
was  subsequently  changed  to  acetoacetic  ester. 

But  in  a  subsequent  paper l  Geuther  pointed  out  that  he  had  failed 
to  isolate  either  the  mono-  or  di-sodium  acetic  ester  ;  but  had  found 
that  a  considerable  quantity  of  acetoacetic  ester  is  formed  by  the 

»  Zeil.  Chem.,  1868,  652. 


222  CHAIN  AND   RING   FORMATION 

action  of  sodium  ethoxide  on  ethyl  acetate,  a  reaction  which  he 
represented  as  follows : 

2C4H  A  +  C2H5ONa  =  C6H9Na03  +  2C2H5OH 

He  observed  at  the  same  time  that  when  the  ethyl  derivative  of 
acetoacetic  ester  is  heated  with  sodium  ethoxide,  ethyl  butyrate  is 
produced.  It  is  therefore  unnecessary  to  assume  the  formation  of 
the  monosodium  compound  of  ethyl  acetate,  since  the  presence  of 
sodium  ethoxide  alone  will  explain,  in  accordance  with  Geuther's 
original  equation,  the  formation  of  both  acetoacetic  ester  and  ethyl 
butyrate.  The  production  of  diethylacetic  ester  and  diethylacetoacetic 
ester  (Frankland  and  Duppa's  diethacetone  carbonate  of  ethyl)  still 
remained  unexplained.  In  a  paper  published  in  1877  by  J.  Wisli- 
cenus,1  the  whole  subject  was  submitted  to  a  critical  re-examination 
with  results  which  have  proved  of  the  highest  importance  to  syn- 
thetical organic  chemistry.  Wislicenus  showed  that,  although  only 
one  atom  of  hydrogen  in  acetoacetic  ester  can  be  replaced  by  sodium 
by  the  direct  action  of  the  metal,  or  of  sodium  ethoxide,  an  alkyl 
group  having  been  introduced  in  place  of  this  atom  of  sodium,  the 
compound  acquires  the  property  of  exchanging  a  second  atom  of 
hydrogen  for  sodium,  which  can  be  replaced  by  a  second  alkyl  group. 
Wislicenus,  adopting  Frankland's  formula,  represented  the  changes 
as  follows : 

CH3 .  CO  .  CHNa .  COOC2H5  +  C2H5I 

=  CH3  .  CO'.  CH(C2H5) .  COOC2H5  +  Nal 

CH3 .  CO .  CNa(C2H5) .  COOC2H5  +  C2H5I 

=  CH3 .  CO  .  C(C2H5)2 .  COOC  JI5  +  Nal 

As  the  second  product  yields,  with  sodium  ethoxide,  diethylacetic  ester, 
Frankland  and  Duppa's  assumption  of  a  disodium  acetic  ester  proved 
as  unnecessary  as  that  of  the  monosodium  compound. 

But  Wislicenus's  inquiry  was  not  limited  to  unravelling  Frankland 
and  Duppa's  experiments.  The  knowledge  of  the  numerous  trans- 
formations which  acetoacetic  ester  undergoes,  the  formation  of  mono- 
and  di-alkyl  derivatives,  the  conditions  which  determine  the  ketonic 
and  acid  hydrolysis,  and  the  synthetic  method  for  preparing  acids 
and  ketones  by  a  combination  of  the  two  processes,  are  due  to  him, 
and  now  belong  to  the  most  familiar  synthetic  reactions  in  organic 
chemistry.  Although  Wislicenus  accepted  Frankland's  formula  for 
acetoacetic  ester  in  opposition  to  Geuther's,  as  the  most  simple 
explanation  of  its  behaviour,  he  did  not  succeed  in  throwing  any 
new  light  on  the  manner  in  which  acetoacetic  ester  is  produced. 
1  Annakn,  1877,  180,  163. 


THE   ACETOACETIC  ESTER  CONDENSATION        223 

Geuther,1  who  regarded  both  the  sodium  compound  and  the  free 
ester  as  possessing  the  hydroxyl,  or,  as  we  now  say,  the  enolic 
structure,  explained  the  process  in  the  following  manner  : 

CH3  .  COOC2TI5  +  2Na  =  CII3  .  C  .  ONa  +  C2H5ONa 
CH3  .  C  .  ONa  +  CH  ,  .  COOC2H5  =  CH3  .  C(ONa)  :  CH  .  COOC2H5  +  H2 
CH3  .  C(ONa)  :  CH  .  COOC2H5  +  C2H4O2 

=  CH3  .  C(OH)  :  CH  .  COOC2H5  +  CH3  .  GOONa 

Frankland  and  Duppa,2  on  the  other  hand,  represented  the  reaction 
as  due  to  the  formation  of  a  sodium  compound  of  acetic  ester,  which 
then  united  with  a  second  molecule  of  acetic  ester, 

CH3  .  COOC2H5  +  CH2Na  .  COOC2H5 

=  CH  ,  .  CO  .  CHNa  .  COOC2H5  +  C2H5OH 

CH3  .  CO  .  CHNa  .  COOC2H5  +  C2H402 

=  CH,  .  CO  .  CH2  .  COOC2H5  -f  CH3  .  COONa 

The  controversy  which  the  structure  of  acetoacetic  ester  aroused, 
and  out  of  which  the  theory  of  tautomerism  was  ultimately  evolved 
(Part  II,  chap,  vi),  diverted  attention  for  a  time  from  the  mechanism 
of  the  reaction.  In  the  meanwhile,  Frankland's  ketonic  formula  for 
both  the  free  ester  and  sodium  compound,  which  expressed  in  a 
simple  fashion  the  greater  number  of  its  transformations,  was 
generally  accepted. 

The  first  serious  contribution  to  a  theory  of  the  acetoacetic  ester 
synthesis  is  contained  in  a  paper  by  Claisen3  published  in  1887,  in 
which  he  shows  that  benzyl  benzoate  unites  with  sodium  methylate 
and  methyl  benzoate  with  sodium  benzylate  to  form  the  same 
additive  compound. 

X)Na 

CCH5  .  COOC7H7  -f  NaOCH3  =  C6H5  .  Q-OCH3 

\OC7H7 


C6H5  .  COOCH3  +  NaOC7H7  =  C6H5  .  C—  OCH3 

\oc7H7 

Benzaldehyde  also  produces  the  same  substance  by  the  action  of 
sodium  methylate. 

2C6H5  .  CHO  +  NaOCH3  =  C6H5  .  C(OCH3)(OC7H7)(ONa) 

1  Annalen,  1883,  219,  123. 

3  Phil.  Trayis.,  1866,  156,  37  ;  Annatoi,  1866,  138,  20-4,  328. 

3  Ber.,  1887,  20,  646. 


22i  CHAIN   AND   KING  FORMATION 

On  the  basis  of  this  observation,  Claisen  suggested  that  acetoacetic 
ester  is  produced  in  two  stages.  A  molecule  of  sodium  ethoxide 
unites  with  ethyl  acetate  and  forms  an  additive  compound,  the  latter 
combining  with  a  second  molecule  of  ethyl  acetate  to  form  sodium 
acetoacetic  ester,  with  the  elimination  of  two  molecules  of  alcohol. 


CH3  .  COOC2H5  +  NaOC2H5  =  CH3  .  C-OC2H5 

\)C2H5 
/ONa 
CH3.  C-iOC2H5  +  H2|CH.COOC2H5 


=  CH3  .  C(ONa)  :  CH  .  COOC2H5  +  2C2H5OH 

According  to  Claisen,  therefore,  the  active  agent  in  the  process 
is  not  metallic  sodium,  but  sodium  ethoxide.  This  view  received 
support  from  a  variety  of  independent  observations.  Ladenburg  in 
1870  made  the  interesting  discovery  that  ethyl  acetate,  carefully  freed 
from  alcohol  by  means  of  silicon  chloride,  is  not  attacked  by  sodium 
in  the  cold,  and  only  very  slowly  on  heating.  It  was  also  observed 
that,  when  ethyl  acetate  only  contains  a  trace  of  alcohol,  the  action 
of  sodium  at  the  commencement  is  very  slow,  but  increases  in  vigour 
as  it  proceeds,  a  fact  which  Claisen  ascribed  to  the  liberation  of  con- 
stantly increasing  quantities  of  alcohol,  as  expressed  in  his  equation. 
Moreover,  Claisen's  theory  explained  the  enolic  structure  of  the 
sodium  compound,  which  was  by  this  time  generally  recognized. 
But  the  most  convincing  proof  of  the  active  agency  of  sodium  ethoxide 
was  afforded  by  the  large  number  of  similar  condensations  effected 
between  different  esters  or  between  esters  and  ketones  either  with 
alcohol-free  sodium  ethoxule,  or,  less  frequently,  with  an  alcoholic 
solution  of  sodium  ethoxide  in  place  of  metallic  sodium. 

Some  of  these  reactions  will  now  be  illustrated.  It  may  be  stated 
at  the  outset  that  the  number  of  condensations  effected  with  sodium 
ethoxide  far  exceeds  that  with  metallic  sodium.  Acetic  ester,  how- 
ever, gives  a  very  much  better  yield  with  sodium  than  with  sodium 
ethoxide,  which  even  at  170°  only  produces  about  one  -third  of  the 
theoretical  amount.  Sodium  acts  similarly  with  propionic  and 
"loutyric  ester,  but  with  much  diminished  yields.  These  products  of 
these  two  reactions  have  the  structure, 

CH3  .  CH2  .  CO  .  CH  .  COOC2H5 

CH3 

Propiopropionic  ester. 


THE  ACETOACETIC  ESTER  CONDENSATION        225 
CH3 .  CH2 .  CH2 .  CO .  CH  .  COOC2H6 

C2H5 

Butyrobutyric  ester. 

It  follows,  therefore,  that  the  carbonyl  group  of  the  one  ester  mole- 
cule attaches  itself  to  the  a-carbon  of  the  second,  and  that  the  reaction 
may  be  expressed  in  the  following  general  form  : 

R  R 

R .  CO . OR  +  CH2.  CO  .  OR  =  R.  CO .  CH .  COOR  +  ROH 

Succinic  ester  and  sodium  give  the  interesting  cyclic  compound 
succinosuccinic  ester,  which  on  oxidation  is  easily  transformed  into 
dihydroxyterephthalic  ester : 

CH .  COOC2H5  C .  COOC2H5 

HC|/\C(OH) 

OCX     JCH2  (HO)ci      JcH 

CH .  COOC2H5  C .  COOC2H5 

Succinosuccinic  ester.  Dihydroxyterephthalic  ester. 

If,  however,  it  is  hydrolysed  and  heated  with  sulphuric  acid,  it 
loses  carbon  dioxide  and  gives  a  cyclic  ketone,  which  may  be  reduced 
to  the  alcohol,  converted  into  the  iodide  with  hydriodic  acid,  and 
finally  reduced  with  zinc  and  acetic  acid  to  cyclohexane.1 

CH2 
_^  H2C/\CH.OH 


CH 


CH2  CH2 

HaC/NcHI  H2C/\CH3 

m/-J  PTT  TT  f4  tf^TI 

L/v         >Uxl2  li2vA         J\jO.2 

/HO.  CH« 


Malonic  ester  condenses  with  itself  in  presence  of  sodium,  giving 
phloroglucinol  tricarboxylic  ester,  the  reaction  taking  place  in  two 

steps.2 

1  Baeyer,  Annalen,  1894,  278,  111. 

3  Baeyer,  Ber.,  1885,  18,  3454  ;  Willstatter,  Ber.,  1899,  32,  1272. 
FT.  I  Q 


226  CHAIN  AND   RING   FORMATION 

r /COOC2H6  yCOOC2H5 

C2H5OOCHf <  +  CH2< 

•  \CO.CH2.COOC2H5 

CO    CH.COOC2H5 
=  C2H5OOC.HC/        NcO 

CO~~CH.COOC2H5 

Phloroglucinol  tricarboxylic  ester. 

Other  examples  of  cyclic  compounds  produced  by  internal  con- 
densation are  furnished  by  the  action  of  sodium  on  adipic  or  pimelic 
esters,1 

CH2 .  CH2 .  COOC2H5      CH2— CH .  COOC2H6 

>CO  -fC2H6OH 

CH2 .  CH2 .  COOC2H5      CH2— CH2 

Adipic  ester.  Cyclopentanone  carboxylic  ester. 

and  by  the  internal  condensation  of  y-acetobutyric  ester  which  yields 
dihydroresorcinol.3 

^NTY        SVS~\ 

CH2.CO.CH3 

=     H2C<     ,     >CH2-fC2HJOH 
CH2.COOC2H5 

W.  Wislicenus  has  extended  the  method  to  the  preparation  of 
aldehyde  esters  and  ketonic-dibasic  esters  by  using  formic  ester  on 
the  one  hand  and  oxalic  ester  on  the  other.  Acetone  and  formic 
ester  in  presence  of  sodium  ethoxide  yield  the  sodium  compound  of 
acetylaldehyde,  CH3 .  CO .  CH2 .  CHO,  which,  on  the  addition  of  acetic 
acid,  almost  immediately  undergoes  further  condensation  to  triacetyl- 
benzene. 

CO.CH3  COCH3 

I  I 

CH2  C 

OHC    \3HO  HC,//NcH        +3H,0 

CH3 .  CO .  H2C      /CH2 .  CO .  CH3     CH  4CO .  cl     Jc .  COCH, 


CHO  CH 

Acetylaldehyde.  Triacetylbenzene. 

Acetophenone  and  formic  ester  can  be  converted  in  the  same  way 
into  tribenzoylbenzene.     Formylacetic  ester,  which  is  obtained  by 

1  Dieckmann,  Ber.,  1894,  27,  102. 

2  Vorlander,  Annalen,  1897,  204,  253. 


THE  ACETOACETIC   ESTER  CONDENSATION        227 

condensing  formic  and  acetic  esters  in  presence  of  sodium,  rapidly 
passes  into  triinesic  ester  at  the  ordinary  temperature.1 

3CHO.  CH2.  COOC2H5  -  C6H3(COOC2H5)3  +  3H2O 

Formylphenylacetic  ester,  which  is  prepared  with  sodium  ethoxide 
from  formic  and  phenylacetic  ester,  yields  two  desmotropic  forms 
(Part  II,  p.  333)  but  does  not  undergo  further  condensation.2 

Oxalic  ester  has  been  a  prolific  source  of  new  condensation  products 
owing  to  the  ease  with  which  it  combines,  in  consequence  no  doubt 
of  its  acidic  character.  In  some  cases  an  alcoholic  solution  of  sodium 
ethoxide  in  place  of  the  alcohol-free  substance  is  sufficient  to  induce 
condensation.  A  variety  of  ketonic  cyclic  compounds  have  been 
prepared.  For  example,  by  condensing  glutaric  and  oxalic  ester3  a 
derivative  of  cyclopentane  is  obtained : 

C2H5OOC .  CH2     COOC2H5        C2H6OOC .  CH— CO 

CH2+  j  =  CH2 

C2H5OOC .  CH2     COOC2H5        C2H5OOC .  CH— CO 

Diketo-cyclopentane  dicarboxylic  ester. 

and  by  combining  /3/3-dimethylglutaric  ester  with  oxalic  ester 
Komppa 4  synthesised  diketoapocamphoric  acid  and  later  camphoric 
acid  (Part  III,  p.  242). 

C2H5OOC .  CH2          COOC2H5       C2H5OOC .  CH— CO 


C(CH3)2 


(CH3)2C 


C2H5OOC  .  CH2          COOC2H5        C2H5OOC  .  CH-CO 

Diketo-apocamphoric  ester. 
Acetic  ester  and  oxalic  ester  yield  oxaloacetic  ester, 

C2H5OOC  .  COOC2H5  +  CH3  .  COOC2H6 

=  C2H5OOC  .  CO  .  CH2  .  COOC2H5  +  C2H5OH 

With  mesityl  oxide,  oxalic  ester  gives  mesityloxide-oxalic  ester 
CH3  COOC,H5  CH3 

C  : 


C:CH.CO.CH3  +  COOC,H.     ->    C  :  CH  .  CO  .  CH2CO  .  COOC,H5 
CH3  CH3 

Mesityloxide-oxalic  ester. 

Oxalic  ester  also  readily  condenses  with  propionic  and  normal  butyric 
ester  but  not  with  isobutyric  ester. 

1  Piutti,  Ber.,  1887,  20,  537.  2  Wislicenus,  Ber.,  1887,  20,  2930. 

8  Dieckmann,  Ber.,  1897,  30,  U70.  *  Eer.,  1901,  34,  2472. 

2 


228  CHAIN  AND  RING  FORMATION 

In  the  latter  observation  Claisen  saw  a  confirmation  of  his  theory, 
to  which  we  will  now  return  ;  for  the  structure  of  isobutyric  ester 
does  not  admit  of  the  removal  of  the  two  molecules  of  alcohol  which 
the  interaction  of  the  additive  compound  of  oxalic  ester  with  sodium 
ethoxide  demands. 

ONa          CH3 

C2H5OCO  .  C—  OC2H5  +  CH  .  COOC2H5 
CH 


The  fact  has,  however,  received  a  much  simpler  interpretation  from 
Dieckmann,1  who  has  shown  that  the  more  acidic  the  /?-ketonic  ester, 
the  less  readily  does  it  undergo  acid  hydrolysis  with  sodium  ethoxide. 
Acetoacetic  ester  is  very  slowly  hydrolysed  at  180°  with  sodium 
ethoxide  in  alcoholic  solution  and  is  scarcely  affected  at  the  boiling 
temperature  ;  the  monoalkyl  esters  change  somewhat  more  readily, 
whilst  the  dialkyl  esters  are  completely  hydrolysed  on  warming 
the  alcoholic  solution  containing  a  trace  of  sodium  ethoxide.  The 
catalytic  action  of  sodium  ethoxide  is  explained  by  Dieckmann  by 
supposing  that  a  molecule  of  sodium  ethoxide  and  then  a  molecule 
of  alcohol  are  taken  up  by  the  ester  and  that  the  product  then  breaks 
up,  regenerating  sodium  ethoxide  : 

ONa 

CH3  .  CO  .  CR2  .  COOC2H5  +  NaOC2H5  =  CH3  .  C—  CR2  .  COOC2H5 

\OC2H5 
)Na 


, 

C— 


CH3C—  CR2  .  CO,R  +  C2H5OH  =  CH3C—  OC2H5  +  CHR2  .  C02R 

2H6 


)C2H 
xONa 

CH  .  C—  OC2H5  =  CH3  .  COOC2H5  +  NaOC2H5 


It  is  clear,  therefore,  that  the  apparently  passive  character  of 
isobutyric  ester  is  due  not  so  much  to  its  structure  as  to  the  in- 
stability of  the  condensation  product  with  oxalic  ester.  It  seems 
to  follow  that  the  process  depends  in  some  measure  on  the  acidic 
character  of  the  final  product,  or,  in  other  words,  on  the  stability  of 
the  sodium  compound  of  the  ketonic  ester.  If  this  is  so,  it  explains 
the  remarkable  differences  which  have  been  observed  in  the  effect  of 
the  condensing  agent,  the  velocity  of  the  reaction,  and  the  amount 
of  the  products. 

1  Ser.t  1900,  33,  2670. 


THE  ACETOACETIC  ESTER  CONDENSATION         229 

The  sluggish  action  and  unsatisfactory  yield  obtained  with  propionic 
and  still  more  with  butyric  ester  may  be  due  to  the  more  positive 
character  of  the  product,  whilst  the  readiness  with  which  oxalic  ester 
enters  into  reactions,  especially  with  other  acidic  substances  like 
acetophenone,  may  depend  upon  the  enhanced  stability  of  the  sodium 
compound  of  the  ketonic  ester.  We  are,  in  fact,  dealing  with  a  wide 
range  of  reversible  reactions  in  which  the  balance  changes  first  to 
one  side  and  then  to  the  other. 

We  may  inquire  a  little  more  fully  into  the  mechanism  of  the 
changes  just  described.  From  what  has  been  stated,  one  is  almost 
forced  to  the  conclusion  that  the  use  of  sodium,  of  dry  sodium 
ethoxide  or  its  alcoholic  solution,  and  latterly  of  sodamide,  to  which 
reference  will  be  made  presently  (p.  233),  only  constitutes  different 
modifications  of  the  same  fundamental  process. 

This  in  itself  is  a  strong  argument  in  favour  of  Claisen's  theory. 
Claisen  has  however  withdrawn  somewhat  from  his  original  position. 
In  a  recent  paper l  he  reaffirms  his  view  of  the  role  which  sodium 
ethoxide  plays  in  forming  an  additive  compound,  but  leaves  unde- 
termined the  nature  of  the  succeeding  changes. 

Dieckmann,  by  reversing  the  process  by  which  he  conceives 
hydrolysis  with  sodium  ethoxide  to  be  effected,  explains  the  aceto- 
acetic  ester  synthesis  by  a  series  of  reversible  steps  as  follows : 

/ONa  ,ONa 

CH3C-OC2H5  +  CH3COoC2H5^±CHoC— CH2C02C2H3  +  C2H5OH 


, 
CH3  .  C—  CH2  .  CO.C.H,  ^±  CH3C(ONa)  :  CH  .  CO2C2H5  +  C2H5OH 


This  scheme  at  first  sight  does  not  appear  to  differ  materially  from 
Claisen's  original  conception  :  but  it  implies  that  the  condensation 
does  not  necessarily  involve  both  steps,  and  that  in  some  cases, 
especially  where  ring  formation  is  involved,  the  removal  of  only  one 
molecule  of  alcohol  may  occur  and  determine  the  final  result. 

Claisen's  theory,  even  in  its  modified  form,  has  not  passed  unchal- 
lenged. Nef  2  explains  the  acetoacetic  ester  and  many  other  con- 
densations as  due  to  dissociation  of  hydrogen  from  carbon  in  the 
negative  group  of  one  molecule  and  the  formation  of  an  unsaturated 
group  in  the  second,  under  the  influence  of  the  specific  reagent. 

1  Ber.,  1903,  36,  3674  ;  1905,  38,  709  ;  1908,  41,  12CO. 

2  Annalen,  1897,  298,  213. 


230  CHAIN  AND   RING  FORMATION 

In  the  present  case  Claisen's  additive  compound  is  supposed  to 
lose  alcohol  and  the  unsaturated  group  in  the  nascent  state  to  unite 
with  the  dissociated  acetic  ester  molecule. 

/ONa  /ONa 

CH,  .  C—  OC.,H-,  -*  CH,  .  C<  +  C2H5OH 

\OCH  '  X 


2 


,ONa 

CH2-  C         +  H—  CH2  .  COOC2H,  =  CH3  .  C(ONa)  .  CH2COOC2H5 
'\OC2H5  ^OC.Hs 

->  CH3  .  C(ONa)  :  CH  .  COOC2H5  +  C2H5OH 

The  dissociation  is  enhanced  by  the  presence  of  negative  atoms 
and  groups,  so  that  compounds  containing  carbonyl,  cyanogen,  and 
nitro  groups  more  easily  undergo  condensation.  Malonic  ester,  being 
more  negative,  dissociates  more  easily  into  H  and  CH(COOR)2  than 
acetic  ester  into  H  and  CH2  .  COOR. 

Those  reagents  which  promote  dissociation  —  acids,  alkalis,  metals, 
&c.  —  assist  condensation.  The  same  principle  is  applied  to  other 
condensations. 

The  formation  of  benzoylacetic  ester,  which  cannot  be  well 
explained  by  supposing  that  hydrogen  is  dissociated  from  the 
nucleus  in  benzoic  ester,  is  brought  under  a  different  scheme.  Here 
the  unsaturated  group  is 

yOC2H5 


C0H5.C-0 


which  unites  with  acetic  ester  as  follows : 

C0H5 .  C-O  +  H— CH2 .  COOC2H5  =  C6H5 .  C— OH 

\CH2.COOC2H5 

/>C2H5 
C6H5 .  C— OH  =  CGH5CO .  CH2 .  COOC,H5  +  C2H5OH 


That  the  same  kind  of  reaction  should  necessitate  such  different 
interpretations  seems  scarcely  satisfactory. 

Michael1   has   opposed   Claisen's   theory  for  many  and   various 
1  J.prakt.  Chem.,  1888  (2),  37,  507 ;  Ber.,  1900,  33,  3731 ;  1905,  38,  1922. 


THE  ACETOACETIC  ESTER  CONDENSATION        231 

reasons,  but  chiefly  on  the  ground  that  no  additive  compound  such 
as  Claisen  describes  has  been  isolated  ;  that  there  is  no  evidence  that 
it  exists  ;  that,  moreover,  the  yield  of  acetoacetic  ester  is  much 
diminished  by  substituting  sodium  ethoxide  for  sodium,  whereas  the 
reverse  would  be  anticipated. 

The  formation  of  such  an  intermediate  additive  compound  is  also 
out  of  harmony  with  his  'neutralisation  law'.  This  law,  which 
is  based  on  energy  changes,  has  already  been  discussed  (p.  113). 
Michael  is  perhaps  more  formidable  as  a  critic  than  as  a  theorist,  for 
his  own  explanation  has  a  weak  point,  inasmuch  as  he  draws  a 
distinction  between  the  mechanism  of  the  change  effected  by  sodium 
and  that  produced  by  sodium  ethoxide.  The  explanation  having 
reference  to  sodium  is  briefly  as  follows.  The  sodium,  which  is  rich 
in  positive  potential  energy,  replaces  hydrogen  in  acetic  ester  and 
gives  rise  to  the  compound  CH2Na .  COOC2H5,  which  isomerises  at 
once  to 

CH, :  C(ONa)OC2H5 ; 

but  the  positive  energy  of  the  sodium  is  still  unexhausted,  and,  in  the 
next  phase,  the  sodium  acetic  ester,  which  still  possesses  free  positive 
energy,  seizes  on  the  carbonyl  group  of  acetic  ester,  containing  free 
negative  energy,  whereby  the  metal  is  so  far  neutralised  that  further 
condensation  stops. 


>ONa  .,0 

CH2  :  C  +  CH3  .  C  =  CH3  .  C-CH2  .  COOC2H5 

\)CH 


Finally,  a  molecule  of  alcohol  is  detached.  The  above  change  cannot 
be  effected  by  sodium  ethoxide,  as  it  possesses  less  free  energy  than 
metallic  sodium. 

It  will  be  seen  that  so  far  as  the  acetoacetic  ester  synthesis  is 
concerned  there  is  no  essential  difference  between  the  views  of 
Michael  and  Nef.  According  to  Michael,  where  sodium  ethoxide 
is  used,  a  process  of  polymerisation  similar  to  the  aldol  condensation 
is  induced  (see  p.  237).  This  condensation  is  brought  about  by  the 
free  energy  of  the  carbonyl  group  in  the  one  molecule  and  the 
mobility  of  the  hydrogen  atom,  due  to  the  proximity  of  a  negative 
group,  in  the  other  molecule.  Thus,  the  union  of  acetic  and  oxalic 
ester  will  be  formulated  as  follows  : 

*  J.  prakt.  Chem.,  1388  (2),  37,  507  ;  1899  (2),  60,  286,  409. 
2  Ber.  1900,  33,  3731  ;  1905,  38,  1922. 


232  CHAIN  AND   RING  FORMATION 

ROOC .  COOR  +  CH3 .  COOR  =  ROOC .  C CH2 .  COOR 

\OC2H5 

The  product  then  interacts  with  sodium  ethoxide  and  a  molecule  of 
alcohol  is  finally  detached. 

/°Na 
ROOG.C CH2.COOR  ->   ROOC . C(ONa) :  CH  .  COOR 

\OC2H5 

In  the  acetoacetic  ester  synthesis  the  sodium  compound  is  formed 
previous  to  condensation ;  in  the  oxaloacetic  ester  it  takes  place  after 
condensation. 

A  very  ingenious  and  suggestive  explanation  of  this  and  other 
condensations  has  been  advanced  byLapworth.1  Lapworth  supposes 
that  the  substance  undergoes  ionisation,  forming  an  equilibrium 
mixture  of  ions. 

Acetic  ester  will  yield  the  following  ions : 

— CH2.C<f  +H  ±£  CH2:C/  +H 

\OC2H6  XOC2H5 

The  presence  of  a  base,  by  diminishing  the  concentration  of  the 
hydrogen  ions,  will  increase  that  of  the  negative  ions  and  accelerate 
the  change.  The  first  represents  the  negative  ion  of  an  organo- 
metallic  compound.  Being  a  weak  ion  it  is  capable,  by  reason  of 
its  electro-affinity,  of  uniting  with  a  neutral  component,2  i.e.  a  mole- 
cule of  acetic  ester,  and  of  a  new  complex  negative  ion  thus  : 


Cxlg  .  C — OC2Hjj 

\3H2.COOC2B5 

The  process  may  be  compared  with  that  by  which  the  alkyl  group  of 
a  magnesium  alkyl  halide  attaches  itself  to  the  carbon  of  a  carbonyl 
group.  The  process  being  reversible,  as  Dieckman  has  shown  (p.  229), 
the  ion  may  lose  its  neutral  component  and  break  up  into  two  mole- 
cules of  acetic  ester,  or  it  may  form  a  neutral  substance  with  a  positive 
ion,  such  as  sodium,  or  it  may  lose  the  negative  ion,  — OC2H5,  in  the 
form  of  alcohol,  and  give  acetoacetic  ester. 

1  Trans.  Chem.  Soc.,  1901,  79,  1269 ;  1902,  81,  1512 ;  Proc.  Chem.  Soc.,  1903,  19, 
190. 
&  See  Abegg  and  Bodliinder,  Zeit.  anorg.  Chem.,  1899,  20,  475. 


THE  ACETOACETIC   ESTER  CONDENSATION        233 

Lapworth  has  shown  the  close  analogy  existing  between  the  aceto- 
acetic  ester  condensation  and  the  Grignard  and  Reformatsky  re- 
actions by  condensing  oxalic  ester  and  bromacetic  ester  in  presence 
of  zinc  or  magnesium,  in  the  manner  already  referred  to  on  p.  218. 

Before  concluding  the  subject  of  the  acetoacetic  ester  synthesis 
reference  should  be  made  to  the  introduction  by  Claisen  of  sodamide 
as  a  condensing  agent.1  In  the  majority  of  cases  its  action  is  quieter 
and  more  regular  than  either  sodium  or  sodium  ethoxide.  It  can  be 
used  in  the  synthesis  of  1 .  3  diketones  and  for  alkylating  ketones. 
Acetophenone  and  ethyl  iodide  in  presence  of  sodamide  give  ethyl- 
acetophenone.  By  the  action  of  ethyl  chloracetate  on  ketones,  glycide 
esters  are  formed.  The  latter  reaction  is  explained  by  Claisen  as 
proceeding  in  three  phases.  In  the  first  an  additive  compound  with 
sodamide  is  formed,  which  undergoes  condensation  with  the  ethyl 
chloracetate  and  is  followed  by  the  removal  of  sodium  chloride. 

1.  CcH5.C(CH3)(ONa).NH2 

2.  CGH5.C(CH3)(ONa)CHCl.COOC2H5 

3.  CCH5.C(CH3)CH.COOC2H5 


O 

Modified  Acetoacetic  Ester  Synthesis  (— COOC2H-  + CH2X  ; 
X  =  CO,  CN,  &c.).  It  is  not  essential  that  the  second  member  taking 
part  in  the  above  condensation  process  should  also  be  an  ester.  The 
place  of  carbethoxyl  may  be  taken  by  a  variety  of  negative  groups, 
such  as  CO  in  aldehydes  and  ketones  and  CN  in  methyl  cyanide 
and  its  derivatives.  The  following  examples  will  illustrate  these 
modifications. 

By  combining  acetic  ester  with  acetone,  acetylacetone  may  be 
prepared. 
CH3  .C02C2H5  +  CH3.  CO .  CH3  =  CH3. CO. CH2 .  CO . CH3  +  C2H5OH 

Acetylacetone. 
Benzoic  ester  and  acetone  form  benzoylacetone. 

CCH5.CO.CH2.CO.CH3 

Benzoylacetophenone   (dibenzoylmethane)   is  formed    in   a  similar 
manner  from  benzoic  ester  and  acetophenone. 

CCH5.CO.CH2.CO.CGH5 

A  variety  of  other  compounds  have  been  obtained  by  Claisen  in  a 
similar  way. 

1  Ber.,  1905,  38,  693. 


234  CHAIN  AND   RING  FORMATION 

Ring  formation  is  illustrated  by  the  linking  of  oxalic  ester  with 
dibenzyl  ketone.1 

C6H5 


COOC2H:>  CH2  CO— CH.C6H5 

+  \CO        =  \CO     +2C2H5OH 

COOC2H5  CH2  CO— CH .  CGH5 

CGH5 

Oxalic  ester  also  condenses  in  presence  of  sodium  ethoxide  with 
methyl  cyanide 2  and  benzyl  cyanide,3  the  first  reaction  taking  place 
as  follows  : 


COOC2H5  COOC2H5 


COOC2H5  +  CH3 .  CN      CO .  CH2 .  CN 

and  the  second, 

/CN 
COOC,H,     CGH5CH2CN         CO .  CH/ 


C2H5OH 


COOC9H5     C6H5CH,CN         CO.CH/' 

\n  i 


5  +  2C9H,OH 


but  the  most  interesting  reactions  of  this  type  are  those  in  which 
formic  ester  is  employed. 

W.  Wislicenus4  was  the  first  to  combine  formic  ester  with 
ketones,  and  obtained  with  acetone  and  acetophenone  the  formyl 
derivatives  already  referred  to  (p.  226).  Formic  ester  also  combines 
with  hippuric  ester,5 

/NH.COC.HS 

H.COOC2H5 


XNH.COC6H5 

=  IICO.CH<  -!-CoH5OH 

\COOC2H5 

and  with  methyl  indole,  in  which  the  CH2  group  derives  its  negative 
character  from  the  proximity  of  the  double  bond.6 

1  Claisen,  Ber.,  1894,  27,  1353. 

2  Fieischhauer,  ,7.  prakt.  Chem.,  1893,  47,  44. 
8  Volhard,  Annalen,  1894,  282,  4. 

4  See  also  Claisen,  Annalen,  1894,  281,  306. 

5  Erlenmeyer,  Ber.,  1902,  35,  3769. 

«  Angeli  and  Marchetti,  Atti  R.  Accad.  Lincei,  1908,  10,  790. 


MODIFIED  ACETOACETIC   ESTER  SYNTHESIS       235 

CH2  CH.CHO 

C6H /\C .  CH3  +  H .  COOC2H5  =  C6H4<f">C .  CH3   +  C2H3OH 


Condensations  with  1  .  3-Diketones,  Claisen's  Method.  In 
studying  the  action  of  formic  ester  on  camphor  in  presence  of  sodium 
alcoholate,  Claisen l  obtained  JiydroxymetJiykne  camphor. 

p-TT  p  .  r»TT     OfT 

Vs&u\   I     2+  HCOOCoH5  =  C8HU/  |  '  4  C,H5OH 

Nx>  \oo 

Camphor.  Hydroxymethylene  camphor. 

The   condensation   product   possesses  strongly  acid   properties  and 
forms  salts  and  esters  after  the  manner  of  acids. 

XC:CH.OM  /CiCH.OR 


With  acetic  anhydride  and  benzoyl  chloride  it  yields  an  acetyl  and 
benzoyl  derivative.  But  the  most  significant  reactions  occur  with 
phosphorus  trichloride  and  the  bases,  ammonia,  aniline  and  methyl- 
aniline.  In  the  first  case  the  hydroxyl  is  replaced  by  chlorine,  in 
the  second,  by  the  radicals  of  the  three  basic  groups  forming  amides. 
It  follows,  therefore,  that  the  new  carbon  group  contains  hydroxyl, 
and  since  it  can  only  be  represented  by  the  unsaturated  group 
=  CH(OH),  the  term  liydroxymetliylcne  has  been  given  to  it.  The 
results  of  this  research  led  to  the  discovery  of  other  hydroxymethylene 
compounds  possessing  still  more  marked  acid  properties.  By  the 
action  of  acid  chlorides  on  acetoacetic  ester  or  its  metallic  compounds 
the  acyl  group  may  replace  hydrogen  either  in  the  methylene  group 
of  the  keto  form,  or  in  the  hydroxyl  group  of  the  enol  form.2  Since 
no  acid  chloride  of  formic  acid  exists,  the  simplest  of  the  acyl 
derivatives,  namely  formylacetoacetic  ester,  could  not  be  obtained  in 
this  way.  Formic  ester,  which  might  be  employed  as  a  substitute  for 
the  acyl  chloride,  does  not  condense  with  acetoacetic  ester  in  presence 
of  sodium  ethoxide,  owing  no  doubt  to  the  formation  of  the  sodium 
compound  of  acetoacetic  ester,  which  would  inhibit  any  further 
reaction.  This  suggested  the  use  of  orthoformic  ester,  but  this 
substance  in  presence  of  acetyl  chloride  condenses  in  the  following 
unexpected  fashion,  giving  diethoxybutyric  ester.3 

1  Annalen,  1894,  281,  306. 

2  The  replacement  of  the  radical  in  the  hydroxyl  of  the  enol  form  is  best 
accomplished  by  means  of  the  acyl  or  alkyl  halide  in  presence  of  pyridine. 

3  Btr.,  1893,  26,  2729. 


236  CHAIN   AND   RING   FORMATION 

CH3  CH3 

I  I  XOC2H5 

CO  C2H50V  C<  +  HCOOC2H5 

|  +    '          >CHOCJ15  =  |  \OC2H5 

PTT  r<  TT  n/  r<u 

V^J12  V2Il5V/  \j£l<£ 

COOC2II,  COOC2H5 

Diethoxybutyric  ester. 

The  latter,  on  distillation,  loses  a  molecule  of  alcohol  and  forms  eth- 
oxycrotonic  ester,  the  isomer  of  ethylacetoacetic  ester. 

CH3 .  C .  CH2 .  C02C2H5  =  CH3 .  C(OC2H5) :  CH .  C02C2H,  +  C,HaOH 


If,  however,  acetic  anhydride  is  employed  as  condensing  agent,  the 
following  reaction  occurs,  which  is  shared  by  other  1 , 8  diketones, 
such  as  malonic  ester,  acetylacetone,  &C.1 

CO  CO 


H2  +  >CHOC,H-  =  C  :  CH  .  OC,H5  +  2C2H5OH 

i       C2H,(K  I 

CO  CO 

I  I 

These  substances  represent  esters  of  strong  monobasic  acids,  for  they 
are  hydrolysed  by  either  water  or  alkalis  yielding  the  free  acid  or  its 
salt,  and  are  converted  into' amides  by  ammonia  or  amines.  The 
strength  of  the  acids,  as  determined  from  their  electrical  conductivities, 
is  of  the  order  of  acetic  acid.  Claisen  concludes  that  the  group 

CO  —  C — CO,  which  is  present  in  these  substances,  may  play  the  part 
of  the  =  0  atom  in  a  carboxylic  acid,  a  view  which  is  readily  under- 
stood by  a  comparison  of  the  two  atomic  groupings,  the  dotted  line 
enclosing  the  equivalent  of  the  doubly  linked  oxygen  in  formic  acid. 


jCO— C— CO;  O 

CH.OH  CH.OH 

Ilydroxymethylene  diketone.          Formic  acid. 

The  presence  of  the  hydroxymethylene  group  in  these  compounds 
is  proved,  as  in  hydroxymethylene  camphor,  by  the  action  of  phos- 
phorous chloride,  which  removes  hydroxyl,  giving  the  acid  chloride. 

CO-C— CO 

CHC1 

i  Annalen,  1897,  297,  1. 


CONDENSATIONS  WITH   1.8  DIKETONES          237 

On  heating  the  latter  with  the  sodium  salt  of  the  acid,  a  compound 
having  all  the  characteristics  of  an  anhydride  is  produced.  The  free 
acids  rapidly  absorb  oxygen  and,  on  warming,  evolve  carbon  dioxide, 
when  the  original  diketone  is  regenerated. 

—CO.  —GO. 

>C :  CHOH  +  O  =  >CH2  +  C02 

—CO/  —CO/ 

The  compounds  undergo  various  other  interesting  changes,  for  an 
account  of  which  the  original  paper  must  be  consulted. 

The  use  of  aldehydes  and  ketones  as  participating  members  in  a 
condensation  introduces  a  whole  series  of  closely  related  reactions, 
among  which  are  included  the  aldol  condensation,  Claisen's  reaction, 
and  the  benzoin  condensation.  These  reactions  can  only  be  treated 
in  a  very  general  way.  It  should  be  noted  that  although  the 
mechanism  of  the  change  is  probably  closely  related  to  that  of  the 
acetoacetic  ester  synthesis  and  allied  reactions,  the  result  in  the 
majority  of  cases  is  essentially  different,  inasmuch  as  it  leads 
indirectly  to  the  separation  of  water  and  the  formation  of  a  double 
bond  between  the  newly  attached  carbon  atoms. 

The  Aldol  Condensation  (CO  +  CH2.CO).  This  condensation, 
which  was  discovered  by  Wurtz,1  occurs  between  aldehydes  and 
ketones,  and  may  be  expressed  by  the  following  general  scheme : 

HC  :  0  -f  CH9 .  C  :  O  =  HC(OH) .  CH .  C*.O 

ill  i  ii 

A  second  phase  in  the  process  results  in  the  elimination  of  water  and 
the  production  of  an  unsaturated  compound. 

HC(OH).CH.C:0  =  CH  :  C.  C  :  O-f  H2O 

i  ii  ill 

The  first  is  the  aldol,  the  second  the  crotonaldehyde  condensation. 
Sometimes  the  first  phase  does  not  appear  and  only  the  second  becomes 
manifest. 

The  usual  reagents,  which  effect  the  condensation,  are  hydrochloric 
acid,  potassium  carbonate,  potassium  cyanide  or  caustic  soda  solution, 
and  less  frequently  sulphuric  acid,  acetic  acid,  acetic  anhydride,  and 
zinc  chloride. 

The  type  of  all  these  condensations  is  the  formation  from 
acetaldehyde  of  aldol  (hydroxybutylaldehyde)  and  crotonic  aldehyde. 
The  first  reaction  occurs  in  presence  of  hydrogen  chloride  or  potas- 
sium carbonate,  and  the  second  either  by  the  action  of  heat  on  the 
aldol,  or  by  the  direct  action  of  zinc  chloride  on  acetaldehyde.  Aldol 

1  Jdhretib..  1872,  449. 


238  CHAIN  AND   RING   FORMATION 

will  condense  again  with  itself,  giving  normal  octylaldol,  as  Raper 
found.1 

CH3 .  CH(OH) .  CH2 .  CH(OH) .  CH2 .  CH(OH) .  CH2 .  CHO 

Octylaldol. 

The  production  of  mesityl  oxide  and  phorone  by  the  action  of  hydrogen 
chloride  on  acetone 2  is  another  example  of  the  crotonaldehyde  con- 
densation. 

CH3  CH3 

CO  +  CH3.  CO.  CH3  =       C  :CH.  CO.  CH3 
CH^ 

Mesityl  oxide. 

CH3  CH3     CH3  CH3 

C:CH:CO.CH3-fCO    =        C:CH.CO.CH:C 

/  \  /  \ 

CH3  CH3     CH3  CH3 

Phorone. 

The  reaction  has  also  been  used  for  preparing  unsaturated  cyclic 
compounds.  Diacetylbutane  and  strong  sulphuric  acid  yield  methyl- 
cyclopentene  methyl  ketone.3 


2 .  CH2 .  CO  .  CH3  ,CH2 .  C .  CO .  CH3 

CH2  ->    CH2 

\CH2 .  CO .  CH3  \CH2 .  C .  CH3 

Diacetylpentane  gives  in  the   same  way  methyltetrahydrobenzene 
methyl  ketone.4 

Claisen's  Reaction.  A  special  interest  attaches  to  the  use  of 
dilute  sodium  hydroxide  solution  as  condensing  agent,  which  was 
first  employed  by  Schmidt5  and  afterwards  studied  by  Claisen.6 
Condensations  between  aldehydes  and  a  variety  of  aldehydes  and 
ketones  have  been  effected  by  this  reagent.  The  syntheses  of  erythrose 
from  glycollic  aldehyde  and  fructose  from  glycerose  furnish  examples 
of  this  process  (Part  III,  p.  6). 

CH2(OH)CHO  +  CH2(OH)CHO  =  CH2(OH) .  CH(OH) .  CH(OH) .  CHO 

Glycollic  aldehyde.  Erythrose. 

1  Raper,  J.  Amer.  Chem.  Soc.,  1907,  91,  1831. 

2  Baeyer,  Annalen,  1866,  140,  297. 

3  Marshall  and  Perkin,  Trans.  Chem.  Soc.,  1890,  57,  241. 

4  Kipping  and  Perkin,  Trans.  Chem.  Soc.,  J890,  57,  14. 

5  Ber.,  1880, 13,  2342.  «  Ber.,  1881,  14,  2471. 


CLAISEN'S  KEACTION  239 

In  many  cases  the  aldol  phase  is  lost,  and  only  the  second  phase 
appears.  Claisen  found  that  benzaldehyde  and  acetone  in  presence 
of  sodium  hydroxide  solution  (10  per  cent.)  yield  benzylidene  and 
dibenzylidene  acetone. 

C6H,CHO  +  CH3 .  CO .  CH3  =  CGH5  .  CH  :  CH .  CO .  CH3  +  H2O 

Benzylidene  acetone. 

CCH5CH:CH.CO.CH3+OHCCGH5  -»  C6H5CH:CH.CO.CH:CHC6H5 

Dibenzylidene  acetone. 

With  o-nitrobenzaldehyde  and  acetone,  Baeyer  and  Drewsen1 
succeeded  in  arresting  the  action  at  the  first  stage  and  obtained  the 
nitrophenyllactyl  methyl  ketone,  which  by  boiling  with  acetic  anhy- 
dride is  converted  into  the  unsaturated  compound. 

N02CGH4CHO  -f  CH3 .  CO .  CH3  ->  N02C6H4CH(OH)CH2COCH3 

Nitropheiiyllactyl  methyl  ketone. 

-»    NO2C6H4CH  :  CH .  CO .  CH3 

Nitrobenzylidene  acetone. 

In  this  condensation  an  excess  of  alkali  is  to  be  avoided,  otherwise 
indigo  is  formed. 

If  the  new  compound  obtained  by  means  of  this  reaction  is  an 
aldehyde,  like  cinnamic  aldehyde  (which  is  formed  from  benzaldehyde 
and  acetaldehyde),  the  process  of  condensation  may  be  repeated. 

C6H5CHO  +  CH3 .  CHO  =  C6H5 .  CH  :  CH .  CHO  +  H2O 

As  Einhorn  and  Diehl2  have  shown,  cinnamic  aldehyde  may  un- 
dergo a  second  condensation  with  another  molecule  of  acetaldehyde 
or  acetone. 

C6H5CH  :  CH .  CHO  +  CH3 .  CHO  ->  C6H6CH  :  CH .  CH  :  CH .  CHO 

This  method  of  condensation  has  received  an  interesting  technical 
application  in  the  preparation  of  ionone — a  substitute  for  essence  of 
violets,  the  sweet-smelling  principle  of  which  it  closely  resembles 
both  in  structure  and  perfume.  Ionone  was  prepared  by  Tiemann 
and  Kriiger3  from  citral,  an  aldehyde  contained  in  citron  and  lemon- 
grass  oil  (Part  III,  p.  257).  Citral  and  acetone  condense  in  presence 
of  baryta  solution  to  form  pscudo-ionone,  which  is  converted  in  turn 
into  a  mixture  of  a-  and  /?-ionone  on  boiling  with  sulphuric  acid. 

(CH3)2C  :  CH .  CH2 .  CH2 .  C(CH3) :  CH .  CHO  +  CH3 .  CO .  CH3  -> 
(CH3)2C :  CH .  CH2 .  CH2 .  C(CH3) :  CH  .  CH  :  CH .  CO .  CH3 

The  conversion  of  pseudo-ionone  into  a-  and  /3-ionone  may  be  sup- 

»  Bcr.,  1882, 15,  2857.  2  £<;/-.,  1885,  18,  2320. 

3  Ber.,  189S,  31,  808. 


240  CHAIN  AND   RING  FORMATION 

posed  to  take  place  by  the  addition  and  subsequent  removal  of  two 
molecules  of  water. 

r*tr    r<TJ 
v/xio  v^.n3     . 

C(OH) 
H2C/    ,CH2.CH:CH.CO.CH3 

H2cl      Jc(OH)CH3 
CH2 

/  \ 

CHa  CH3  CH3  CH3 

C  C 

.  CH :  CH  .  CO .  CH3    H2C/\C .  CH  :  CH .  CO .  CH3 

).CH3  H2<\  Jc.CH3 


H 

a-Ionone.  $-Ionone. 

Irone,  the  perfume  itself,  is  represented  by  the  formula 

CH3 


Y 


HCCH  .  CH  :  CH  .  CO  .  CH 


Another  example  of  cyclic  formation  is  furnished  by  the  conversion 
of  citronellal  into  isopulegol.2 

(CH3)2 :  CH .  CH2 .  CH2 .  CH(CH3) .  CH2 .  CHO 

CH2  CH2 

=  (CH3)2C:C/      "\CH.CH3 
(HO)HC       CH2 

Like  the  aldehydes,  diketones  may  undergo  condensation  with  other 
ketones,  and  Japp 3  and  others  have  succeeded  in  forming  products 
by  combining  benzil  and  phenanthraquinone  with  acetone,  &c.  An 
interesting  application  of  the  same  reaction  is  due  to  von  Pechmann,4 
who  prepared  quinones  of  the  benzene  series  by  a  similar  process. 

1  Ber.,  1891,  26,  2675.  2  Tiemann  and  Schmidt.  Ber.,  189C,  29,  913. 

3  Ber.,  1883,  16,  275,  282.  4  Ber.,  1888,  21,  1417,  1895,  28,  1845. 


CLAISEN'S   REACTION  241 

Thus,  diacetyl  and  sodium  hydroxide  gave  first  the  intermediate 
product  dimethylqu'uwgen  and  by  internal  condensation  p-xyloquinone. 

CH,.CO.CO.CH3  CH3.C.CO.CH3 

+  -»  -* 

CH3 .  CO .  CO .  CH3  HC .  CO .  CO .  CH3 

Diacetyl.  Dimethylquinogen. 

CH3.C.CO.CH3 


.CO.C.CH3 

p-Xyloquinone. 
Acetyl  propionyl  forms,  in  the  same  way,  duroquinone. 

Xnoevenagel's  Reaction  (CO  +  CH2X  ;  X  =  CO  ;  CN  ;  NO2.  &c.). 
Among  the  earlier  attempts  to  bring  about  condensation  of  aldehydes 
and  ketones  with  1 .  3  diketones  and  ketonic  esters  is  that  of  Claisen,1 
who,  by  the  use  of  hydrogen  chloride,  succeeded  in  obtaining  con- 
densation products  with  acetaldehyde,  benzaldehyde,  and  acetoacetic 
ester  of  the  formula  : 


.COOC.H5 
CH3.CO 

Much  more  effective  reagents  for  this  purpose  are  ammonia  and  the 
primary  and  secondary  bases,  and  even  glycocoll  and  other  amiuo 
acids  can  be  used  in  some  cases.3 

Japp  and  Streatfeild 3  were  the  first  to  employ  ammonia  to  condense 
phenanthraquinone  and  acetoacetic  ester. 

/CO.CH3 
C6H4 .  CO  /CO  .  CH3         C6H4  .  C  :  C< 

I   +  CH/  _>  |  \cooan5 

C6H4 .  CO  \COOC2H5        C6H, .  CO 

In  1893  Knoevenagel 4  carried  out  a  much  more  complete  investi- 
gation, in  which  not  only  ammonia,  but  diethylamine,  piperidine  and 
aniline  were  used  with  success.  Thus,  benzaldehyde,  in  presence  of 
small  quantities  of  diethylamine,  condenses  with  acetoacetic  ester 
when  cooled  in  a  freezing  mixture,  forming  benzylidene  acetoacetic 
ester,  that  is,  the  compound  which  Claisen  obtained  with  hydrogen 
chloride. 

,CO.CH3 
CCH5.CH:C<; 

\COOC2H5 

1  Annalen,  1883,  218,  172.  s  Dakin,  Journ.  Biol.  Chem.,  1909,  7,  49. 

s  Trans.  Chem.  Soc.,  1883,  43,  27. 

*  Annalen,  1894,  281,  25 ;  Ber.,  1904,  37,  446. 

PT.  I  & 


i. 

242  CHAIN   AND  KING  FOEMATION 

This  example  may  serve  as  the  type  of  a  very  general  process  in  which, 
on  the  one  hand,  aldehydes  and  ketones  may  be  used,  on  the  other  hand 
a  variety  of  1 .  3  diketones  and  ketonic  esters,  namely  malonic  ester, 
benzoylpyruvic  ester,  benzoylacetic  ester,  acetonedicarboxylic  ester, 
barbituric  acid,  tetronic  acid,  acetylacetone,  benzoylacetone,  cyan- 
acetic  ester,  and  also  succinic  ester.  Stobbe 1  obtained  the  following 
by  condensing  acetone  with  succinic  ester  : 

CH, 

>C:0 

CH2.COOC2H5 


3N>C:C.COOC9H, 
CH 


Acetone  also  condenses  with  cyanacetic  ester.2 

CH3,  ,CX  CH3X  ,CX 

>CXUH2C<  =          >C:C<  +H20 

CH/  \COOC2H5     CH/          \COOC2H5 

Aldehydes  condense  with  cyanacetamide,3 


2.CN->R.CH:C.CN 


CONH2  CONH2 

and  with  indene  as  follows  :  4 

CH2  CH.CH(OH).CCH5 


OH  CH 

Aliphatic    and    aromatic   nitro-compounds   may   replace    the   1.3 
diketone,5 

E.  CHO  +  K1  .  CH2  .  N02  =  KCH  :  CR1  .  N02  +  H20 
and  2  .  4-dinitrotoluene  condenses  with  benzaldehyde, 

CCH5  .  CHO  +  CH3  .  CCH3(N02)2  ->  CCH5  .  CH  :  CH  .  CGH  (N02)2 
Phthalic  anhydride  undergoes  condensation  like  a  ketone.6 

CO  C:CH.N02 

CCH4/\0  +  CH3N02  =  CeH  /  \}  +  H20 

CO  CO 


Ber.,  1893,  26,  2312 ;  1894,  27,  2405. 

Perkin  and  Ha  worth,  Tram.  Chem.  Soc.,  1908,  93,  1944  ;  1909,  95,  480. 

Gabriel,  Ber.,  1903,  36,  570. 

Marckwald,  Ber.,  1895,  28,  1501. 

Ber.,  1899,  32,  1293.  6  Gabriel,  Ber.,  1903,  36,  570. 


KNOEVENAGEL'S  REACTION  243 

In  the  same  category  may  be  included  such  reactions  as  that  of 
benzaldehyde  on  acetic  ester,  giving  cinnamic  ester, 

C6H5 .  CHO  +  CH3 .  COOC2H5  =  C6H  ,CH :  CH  .  COOC2H5  +  H2O 
and  the  condensation  of  a-methylpyridine  and  a-methylquinoline 
with  aldehydes  and  ketones,  the  acidity  of  the  methyl  group  being 
determined  by  the  adjoining  CN  group. 

CH  CH 

HC/V:H  HC/VlH 

HC!  Jc  .  CH3  +  CHO  .  CH3  ^  Hoi     Jc .  CH  :  CH  .  CH3 

N  N 

The  formation  of  leucobenzaldehyde  green  is  another  example  of 
the  same  process. 

C0H5CHO  +  2C0H5N(CH3)2  -»  C6H5.  CH[CGH4N(CH3)2]2 
The  action  of  formaldehyde  requires  special  mention,  since  its 
peculiar  reactivity  causes  it  to  enter  into  a  variety  of  combinations. 
With  malonic  and  acetoacetic  ester  it  behaves  like  benzaldehyde, 
losing  oxygen  and  combining  with  two  molecules  of  the  ester  (see 
below). 

2CH2 .  (COOC2H5)2  +  CH20  =  (C2H5OOC),CH  .  CH2 .  CH(COOC2H-)2 
It  also  unites  with  two  molecules  of  benzene  and  its  derivatives  in 
presence  of  sulphuric  acid  or  other  dehydrating  agent,  with  loss  of 
oxygen,  forming  a  diphenylme thane  compound,1 

2C6H6  +  CH2O  =  C6H5 .  CH2 .  C6H5  +  H2O 

Under  other  conditions  (e.  g.  in  alkaline  solution),  however,  it  under- 
goes the  aldol  condensation.  With  ordinary  phenol  it  forms  a  mixture 
of  ortho  and  para  hydroxy benzyl  alcohol.2 

<H2OH 
H 

With  nitroparaffins  it  behaves  similarly,  two  molecules  of  formalde- 
hyde combining  with  nitroethane  in  the  following  way  : s 

CH3 .  CH2 .  N02  +  2CH20  =  CH3 .  C(CH2OH)2NO2 
and  with  a  picoline  it  forms  the  derivatives 4 

CSH4N .  CH.2(CH2OH)  and  C5H4N .  CH(CH2OH)2 

1  ttaeyer,  1873,  5,  25,  280,  1094;  Simon,  Anntden,  1903,  329,  30;  Boehm,  .Ber., 
1904,  37,  4461. 

2  Manasse,  Ber.,  1894,  2?,  2409. 

8  Henry,  Eec.  trav.  chim.  Pays-Bas.,  1897,  17,  189;    Piloty,  Ber.,  1897,  30,  3161. 
4  Koenigs  and  Happe,  .Ber.,  1902,  35,  1343  ;  1903,  36,  2V.04  ;  Lipp  and  Richard, 
Ber.,  1904,  S7,  7G7. 

B  2 


244  CHAIN  AND   RING  FORMATION 

In  some  cases  two  molecules  of  the  1 .  3  diketone  condense  with 
the  aldehyde  if  the  process  is  conducted  under  modified  conditions. 
Thus,  benzaldehyde  and  acetoacetic  ester  condense  in  presence  of 
diethylamine,  if  the  reaction  proceeds  at  the  ordinary  temperature,  to 
form  benzylidenediacetoacetic  ester. 

CO.CII3 
CH< 

OO  OH  /          M^/OOC  H 

CCH5CHO  +  2CH,/  3  =  CCH5CH(  %  H2O 

\COOC2H5  \         ,CO.CH3 

CH/ 

\COOC2H5 

Compounds  of  this  character,  which  may  be  described  as  1 . 5  di- 
ketones,  are  capable  of  internal  condensation  in  presence  of  alkalis  or 
hydrochloric  acid,  and  a  variety  of  cyclic  compounds  have  been  built 
up  in  this  manner,  of  which  the  following  is  an  example.1  Alkyli- 
denediacetoacetic  ester  undergoes  inner  condensation  with  alcoholic 
potassium  hydroxide,  and,  on  hydrolysis,  loses  carbon  dioxide  and 
yields  the  cyclohexenone  derivative. 

CH3  .  CO .  CH .  COOC,H5  CH3 .  C— CH .  COOC2H5 

->          CH        CHR 


CH3 .  CO  .  CH .  COOC2H5  CO— CH ,  COOC2H5 

CH3.C CH2 

-»     HC/'        \CHR 

concH2 

An  analogous  reaction  to  the  above  is  the  formation  of  isoacetophorone 
from  acetone  and  lime. 

CH3  f  H;CH2 .  CO .  CH3          CH3     CH2 .  CO .  CH, 


H3j   HjCH2.CO.CH3          CH3     CH2.CO.CH3 

Acetone.  Intermediate  product. 

CH3     CH0  CO 


3  2 

C/        ^C 


CH3 

Isoacetophorone. 


1  Annalen,  1894,  281,  25  ;  1895,  288,  321. 


KNOEVENAGEL'S  REACTION  245 

Knoevenagel  explains  the  action  of  the  condensing  agent  on  the 
assumption  that  the  aldehyde  first  unites  with  the  base.  Benzalde- 
hyde  and  piperidine  combine  as  follows  : 

C6H5CHO  +  2C5H10NH  =  C6H5CH(NC5H10)2  4-  H20 

The  product  then  interacts  with  the  diketone  and  regenerates  the 
base,  which  thus  plays  the  part  of  a  catalyst. 

C0H5CH(NC6H10)a  +  CH3 .  CO .  CH2 .  COOC2H5 

/CO.CIL, 

=  C6H5CH:C<  +2C5H10NH 

\COOC2H5 

Another  explanation  based  on  ionisation  (p.  232)  has  been  advanced 
by  Hann  and  Lap  worth,1  in  which  the  acetoacetic  ester  forms  an 
equilibrium  mixture  of  the  following  ions  : 

CH3 .  CO  :  CH .  COOC2H5  +  H  ^±  CH3 .  CO .  CH .  COOC2H5  +  H 

The  latter  would  then  combine  with  the  molecule  of  benzaldehyde 
as  neutral  component  (see  p.  232)  from  which,  by  elimination  of 
a  hydroxyl  ion,  benzylidene-acetoacetic  ester  would  be  produced. 

CH3  .  CO  .  CH  .  COOC.H5  CH3 .  CO .  C .  C002H5 

|      ,  +H-*  ||  +  H.O 

C6H6CHO  C6H5CII 

The  effect  of  the  base  might  be  to  remove  hydrogen  ions  by  forming 
the  complex  NRRH2  or  introduce  hydroxyl  ions  and  thus  increase 
the  concentration  of  the  organic  ions. 

Benzoin  Condensation.  The  action  of  potassium  cyanide  on 
aromatic  aldehydes  is  a  peculiar  one,  and  may  be  represented  by 
the  oldest  example — the  formation  of  benzoin  from  benzaldehyde 
and  alcoholic  potassium  cyanide — which  was  first  studied  by  Liebig 
and  Wohler.2 

C6H5COH  C6H5.CH.OH 

C6H+5COH  C6H5.CO 

Ben/aldehydo.  Benzoin. 

The  reaction  bears  a  close  resemblance  to  the  aldol  condensation. 
The  specific  action  of  the  cyanide,  which  differs  fundamentally  from 
that  of  the  caustic  alkalis  or  sodium  eth oxide  (which  produce  benzyl 
benzoate  or  a  mixture  of  benzyl  alcohol  and  benzoic  acid),  has 
received  various  explanations,8  the  most  plausible  of  which  is  that 

1  Tran*.  CJtem.  Soc.,  1904,  85,  46.          2  Anna'en,  1832,  3,  276. 
8  Knoevenagel,  Ber.,  1888,  21,  1346  ;  Kef,  Annalm,  1897,  298,  312. 


246 


CHAIN  AND   RING  FORMATION 


of  Lap  worth.1  He  suggests  that  the  benzaldehyde  forms  a  cyan- 
hydrin  with  potassium  cyanide,  which  then  condenses  with  another 
molecule  of  benzaldehyde,  hydrogen  cyanide  being  finally  elimi- 
nated. 


C6H5 
I 
HO .  CH     + 


r*  TJ  r*  TT 

C6H5  CCII 

CH  :  O     =     HO .  C — 

CN 


CH.OII 


-o,l- 


CH.OH 


HCN 


Pinacone  Condensation.  A  reaction  not  unlike  that  which  pro- 
duces  aldol  and  benzoin,  and  which  was  first  observed  by  Fittig,2 
is  brought  about  by  the  action  of  neutral,  alkaline,  and  occasionally 
acid  reducing  agents  on  aldehydes  and  ketones.  In  addition  to 
primary  and  secondary  alcohols,  this  reaction  gives  rise  to  substances 
known  aspinaconcs.  In  this  reaction  the  molecules  of  the  original 
compound  become  linked  by  the  aldehyde  or  ketone  carbon  atom  ;  at 
the  same  time  two  atoms  of  hydrogen  are  taken  up.  The  compounds 
are  in  fact  secondary  or  tertiary  glycols.  The  following  examples 
will  illustrate  the  process : 


(LH.COH 


-f  Ho     = 


C6H5COH 

Benzaldehyde. 

CH3.CO.CH3 

+  +H 

CH3.CO.CII3 

Acetone. 


CH.CO.CH 


65 


C6H5.CO.C0H6 

Benzophenone. 


Ho     = 


CGH5CH.OH 


C6H5CH  .  OH 

Hydrobenzoin  (and 
Isohydrobenzoin). 

CH3.C(OH).CH3 
CH3  .  C(OH)  .  CH3 

Tetramethylethylene  glycol. 

C8H5.C(OH).C6H5 
C,H6.C(OH).C6H6 

Benzpinacone 
Tetraphenylethylene  glycol. 


The  first  of  the  above  reactions  occurs  with  aromatic  aldehydes 
and  a  few  of  the  aliphatic  aldehydes  3  ;  the  two  latter  are  alike 
shared  by  aliphatic  and  by  aromatic  ketones.  The  reaction  has  been 


.,  1903,  83,  095. 

2  Annakn,  1858,  110,  26  ;  1859,  114,  54.     The  name  pinacone  has  reference  to 
the  tabular  form  of  the  crystals  obtained  from  acetone  (iriva£  =  table). 

3  Ciusa.  R.  Accad.  Lincei,  1913.  22,  681. 


PINACONE   CONDENSATION  247 

used  for  internal  condensation,  as,  for  example,  in  the  preparation  of 
dimethyldihydroxy-cycloheptane  from  diacetylpentane.1 


H2 .  CH2 .  CO .  CH3  /CH2 .  CH2 .  C(OH) .  CH3 

v  —>    CH2<f 

X)H9.CH2.CO   CH,  xCHo.CH, 


The  reduction  is  usually  effected  by  sodium  amalgam,  the  aluminium- 
mercury  couple,  zinc  and  acetic  acid,  or  zinc  and  hydrochloric  acid. 

No  very  clear  explanation  of  the  mechanism  of  the  process  is  yet 
forthcoming.  The  action  of  sodium  on  aldehydes  and  ketones  has 
been  studied  by  Fittig,  Beckmann  and  Paul,  and  also  by  Freer,  and 
may  possibly  throw  some  light  on  the  subject.  Kane,  early  in  the 
nineteenth  century,  found  that  potassium  liberates  hydrogen  from 
acetone  and  forms  a  compound  C3H5OK,  and  more  recently  Freer 3 
stated  that  he  had  obtained  a  similar  compound  by  the  action  of 
sodium,  to  which  he  assigned  the  formula  CH3 .  C(ONa) :  CH2 . 
Fittig's3  observation  that  sodium  acts  upon  acetone  with  the  pro- 
duction of  a  sodium  compound  of  pinacone  receives  a  ready  inter- 
pretation if  we  assume  that  two  molecules  of  a  nascent  sodium 
acetone  become  linked  in  process  of  reduction. 
CH3.C(ONa).CH3 

CH3  .  C(ONa) .  CH3 

Beckmann  and  Paul 4  have  shown  in  the  same  way  that  benzaldehyde 
and  benzophenone  form  sodium  compounds  which  are  decomposed 
by  water. 

C6H5COH        Na  C6H5CH .  ONa  C6H5CH .  OH 

+          +          -*  +  H.,0    ->     = 

C6H5COH        Na  C6H5CH .  ONa  C6H5CH .  OH 

Benzaldehyde.  Hydrobenzoin. 

(C6H5)2CO      Na  (C6H5)2C.ONa  (C6HJ,C.OH 

+  -»  >0      +H20    -» 

(C6H5)2CO      Na  (C6H5),C.  Na  (°6H^C ' OH 

In  the  latter  case  benzhydrol  is  also  formed. 

According  to  Schlenk5the  formula  of  the  sodium  compound  of 
benzpinacone  has  half  the  molecular  weight  assigned  by  Beckmann 
and  Paul,  and  contains  tervalent  carbon  (p.  65). 

(C0H5)2C.ONa 

1  Kipping  and  Perkin,  Tians.  Chcm.  Soc.,  1891,  59,  214. 

2  Amer.  Chem.  J.,  1893.  15,  582  ;  see  also  Taylor,  Trans.  Clitm.  Soc.,  190C,  89,  125S. 

3  Annalen,  1859,  110,  25  ;   1800,  114,  54. 

4  Annalen,  1892,  260,  1.  5  Btr.,  1911,  44,  1178. 


248  CHAIN  AND   RING  FORMATION 

Perkin's  Reaction.  The  history  of  this  interesting  reaction  dates 
from  Perkin's  synthesis  of  coumarin  in  the  year  1868.1  Coumarin, 
the  sweet-smelling  principle  of  woodruff  and  hay,  was  found  to 
decompose,  on  fusion  with  potassium  hydroxide,  into  salicylalde- 
hyde  and  acetic  acid, 

C9H60,  4-  2H20  =  C7H602  +  C2H402 

Coumarin.  Sal  icy)  aldehyde. 

from  which  the  natural  conclusion  was  drawn  that  coumarin  was 
the  anhydride  of  acetylsalicylaldehyde. 

,CHO  .CO 


i\  — "     ^e^av 

\nn  TT.n  \< 


C6H 

OC2H30  \COCH, 


By  heating  sodium  salicylaldehyde  with  acetic  anhydride,  coumarin 
was,  in  fact,  obtained.  The  evidence  seemed  conclusive  until  it  was 
discovered  that  acetylsalicylaldehyde  is  unchanged  by  acetic  anhy- 
dride, although,  with  the  addition  of  fused  sodium  acetate,  coumarin  is 
readily  produced.  The  formula  assigned  by  Perkin,  which  represented 
coumarin  as  a  derivative  of  acetylsalicylaldehyde,  was  disputed  by 
Fittig,  who  could  not  reconcile  it  with  the  constitution  of  coumaric 
acid,  of  which  it  is  the  anhydride  ;  for  coumaric  acid  must  then  form 
coumarin  by  the  removal  of  hydrogen  from  the  benzene  nucleus, 
a  process  which  seemed  difficult  to  reconcile  with  the  properties  of 
the  compound. 

/COOH  ^CO 

C6H4<  ->    C6H8f 

NX).CH3  XX).CH3 

Fittig  preferred  to  base  his  view  of  its  constitution  on  a  reaction 
discovered  by  Bertagnini 2  for  the  preparation  of  cinnamicacid,  which 
consisted  in  heating  benzaldehyde  and  acetyl  chloride. 

C6H5CflO  +  CH3 .  COgP=  C6H5CH  :  CH .  COOH  +  HC1 


The  formation  of  coumarin  might   be    explained  in  an  analogous 
fashion. 

/ONa      CH3 .  CO.  ,ONa 

C6H4<(          +  \0->C6H4<  +CH3.COOH 

\CHO     CII? .  CO/  \CH :  CH .  COOH 

M 


CGH4<  4  CHo .  COONa-> CGH4  +  HO 

XJH  :  CH .  COOH 

The  formula  for  coumarin  as  the  inner  anhydride  of  o-hydroxycin- 
1  TYans.  Chem.  Soc.,  18C8,  21,  53.  2  Annalen,  1856,  100,  12C. 


PERKIN'S   REACTION  249 

namic  acid  is  now  universally  accepted.1  In  1877"  Perkin  published 
a  new  method  for  preparing  cinnamic  acid  and  analogous  compounds 
by  means  of  a  reaction  of  very  general  application  which  now  bears 
his  name.  It  consists  in  heating  a  fatty  or  aromatic  aldehyde  and 
the  anhydride  of  a  fatty  acid,  together  with  its  sodium  salt,  to  180° 
for  several  hours.  The  formation  of  cinnamic  acid  from  benzalde- 
hyde,  acetic  anhydride,  and  sodium  acetate  was  explained  by  Perkin 
on  the  assumption  that  the  an  hydride  acted  upon  the  aldehyde  in  the 
following  manner : 

CH3.COX          C6H5CH:CH.CON 

2C6H5CHO  +  >0  =  >0  +  2H20 

CH3 .  OCX         C6H5CH  :  CH  .  CO/ 

The  view  was,  however,  opposed  to  the  observation  of  Geuther  and 
Hilbner,  who  found  that  benzaldehyde  and  acetic  anhydride  yield 
benzylidene  acetate : 

CH3.COV  /O.OC.CH3 

C6H, .  CHO  +  >0  =  CCH5 .  CH< 

CH3.CCK  H).OC.CH3 

To  settle  the  question,  Perkin  heated  benzaldehyde  and  acetic 
anhydride  with  sodium  propionate  and  obtained  cinnamic  acid, 
whereas  with  propionic  anhydride  and  sodium  propionate,  phenyl- 
crotonic acid  was  formed.  Perkin  assigned  to  phenylcrotonic  acid 
the  formula, 

C6H5 .  CH  :  CH .  CH2  .  COOH. 

By  the  interaction  of  benzaldehyde,  succinic  anhydride  and  sodium 
succinate,  a  second  or  isophenylcrotonic  acid  was  subsequently  pre- 
pared by  Perkin,  the  formation  of  which  received  the  following 
interpretation  : 

C6H5CHO:  C6H5.CH 

C;H2  COOH     =  C .  COOH  +  H2O  +  C02 

CH2.-COO:H  CH3 

Fittig,8  who  had  been  engaged  in  a  careful  study  of  the  unsaturated 
acids,  was  unable  to  reconcile  the  properties  of  the  two  phenylcrotonic 
acids  with  the  respective  formulae  assigned  by  Perkin.  The  ot/3 
unsaturated  acids  possess  the  following  properties  in  common : 
the  additive  compounds  with  hydrobromic  acid,  when  heated  in 

1  According  to  Michael  (J.  prakt.  Cfiem.,  1899,  60,  3C8)  Strecker  was  the  first  to 
propose  tliis  formula  in  his  Lehrbuch. 

*  Trans.  Chem.  Soc.,  1877,  32,  389.  *  Eer.,  1894,  27,  2G53. 


250  CHAIN  AND  RING   FORMATION 

aqueous  solution,  either  lose  hydrogen  bromide  and  pass  back  into 
the  original  compound,  or  the  bromine  atom  is  replaced  by  hydroxyl, 
whilst  in  alkaline  solution,  carbon  dioxide  and  hydrogen  bromide 
are  removed,  and  an  unsaturated  hydrocarbon  results.  /?-bromo- 
phenylpropionic  acid  reacts  in  the  following  way : 

1 .  C6H5CHBr .  CH2 .  COOH  =  C6H6 .  CH  :  CH .  COOH  +  HBr 

2.  C6H5CHBr .  CH2 .  COOH  +  H2O 

=  C6H5CH(OH) .  CH2 .  COOH  +  HBr 

3.  C6H5CHBr  .  CH2 .  COONa  =  C6H5CH  :  CH2  +  NaBr  +  CO2 

It  was  the  first  and  not  the  second  phenylcrotonic  acid  which  behaved 
in  this  way  and  gave  with  sodium  hydroxide  solution  the  unsaturated 
hydrocarbon,  methylstyrene,  C6H6CH  :  CHCH3.  The  two  formulae 
must  consequently  be  reversed.  It  follows,  therefore,  that  in  the 
reaction  between  benzaldehyde  and  propionic  acid,  it  is  the  a-carbon 
of  the  acid  which  attaches  itself  to  the  carbon  of  the  aldehyde 
group.1 

In  order  to  follow  the  phases  of  the  second  reaction,  Fittig  and 
Jayne2  repeated  Perkin's  experiment  with  benzaldehyde,  succinic 
anhydride,  and  sodium  succinate,  but  at  a  temperature  of  100°  instead 
of  180°,  with  the  following  interesting  results  :  no  carbon  dioxide 
was  evolved,  but  phenylparaconic  lactone  was  formed,  which,  on 
heating,  evolved  carbon  dioxide  and  yielded  isophenylcrotonic  acid. 
Fittig  explained  the  changes  as  follows : 

COOH  COOH 

C6H5CHO  +  CH2.CH2  ->  CCH5CH(OH).CH.CH2  -* 

COOH  COOH 

COOH 

I 
CCH5 .  CH  .  CH .  CH2  ->  C6H5CH  :  CH  .  CH2COOH  +  C02  +  H20 

!  I 

0 CO 

Phenylparaconic  lactone.  Isophenylcrotonic  acid. 

The  production  of  a  hydroxy  compound,  which,  as  in  the  aldol 
condensation,  Fittig  assumed  to  represent  the  first  phase  of  the 
process,  was  rendered  still  more  probable  by  the  formation  of  phenyl- 
hydroxypivalic  acid  from  benzaldehyde  and  sodium  isobutyrate  in 
presence  of  acetic  anhj'dride.3 

1  This  view  had  already  found  expression  in  Mark  own  ikofTs  law,  Annalrn, 
1808,  146,  348,  and  had  been  further  insisted  on  by  Michael  (Ber.,  1878, 11,  1015). 

2  Annalen,  1882,  218,  97.  3  Annakn,  1882,  210,  115. 


PERKIN'S  REACTION  251 

CH3  CH3 

C6H5 .  CHO  +  CH .  COONa  =  CGH5 .  CH(OH) .  C  .  COONa 
CH3  CH3 

Phenylhydroxypivalic  acid. 

Fittig  found,  moreover,  that  in  the  preparation  of  phenylparaconic 
(actone  at  the  lower  temperature,  acetic  anhydride  may  replace  with 
advantage  succinic  anhydride,  and  this  led  him  to  infer  that  it  is  the 
aldehyde  and  the  sodium  salt  which  interact,  and  not,  as  Perkin  had 
assumed,  the  aldehyde  and  anhydride.  By  conducting  the  process 
at  100°  he  in  fact  obtained,  from  benzaldehyde,  sodium  propionate 
and  acetic  anhydride,  phenylcrotonic  acid,  and  from  sodium  butyrate 
and  acetic  anhydride,  phenylangelic  acid.  The  fact  that  Perkin  had 
obtained  cinnamic  acid  from  benzaldehyde,  acetic  anhydride,  and 
sodium  propionate  now  received  a  simple  explanation,  for  if  the 
reaction  is  conducted  at  100°,  the  sodium  salt  of  the  acid  reacts, 
whereas  at  180°  double  decomposition  will  occur  between  the  acetic 
anhydride  and  sodium  propionate  or  sodium  butyrate,  yielding  sodium 
acetate  and  propionic  anhydride  or  butyric  anhydride.  The  sodium 
salt  then  produces,  with  benzaldehyde,  cinnamic  acid.  Fittig's  view 
received  apparent  confirmation  from  the  experiments  of  Stuart,1  who 
prepared  analogous  compounds  with  malonic  and  isosuccinic  acids, 
both  of  which  are  incapable  of  forming  anhydrides.  Fittig  then  drew 
the  following  conclusions :  Perkin's  reaction  occurs  between  the 
aldehyde  and  the  sodium  salt  of  the  acid  in  two  stages  ;  in  the  first 
a  hydroxy  compound  is  formed,  condensation  taking  place  between 
the  aldehyde  and  a-carbon  of  the  acid  ;  in  the  second,  water  is 
eliminated.  In  the  case  of  polybasic  acids  a  lactone  may  be  formed 
from  which  water  and  carbon  dioxide  can  be  removed  on  heating. 
In  spite  of  apparently  convincing  proofs,  Perkin2  did  not  relinquish 
his  original  view  that  the  interaction  takes  place  between  the  anhy- 
dride and  the  aldehyde,  a  view  which  is  also  shared  by  Michael. 
Perkin  pointed  out,  for  example,  that  the  formation  of  phenylangelic 
acid  on  heating  a  mixture  of  benzaldehyde,  sodium  butyrate,  and 
acetic  anhydride  to  100°  does  not  prove  that  combination  occurs 
between  the  aldehyde  and  the  sodium  salt ;  for,  in  the  first  place, 
cinnamic  acid  cannot  be  formed  under  any  circumstances  at  this 
low  temperature,  and  secondly,  the  sodium  salt  and  acetic  anhydride 
react  readily  at  100°  to  form  sodium  acetate  and  butyric  anhydride, 
and  the  same  is  true  of  the  salts  of  other  higher  fatty  acids.3  Perkin 

1  Ber.,  1883,  16,  1436.  2  TranSi  c/im.  SoCtj  1886>  47,  317. 

3  Michael,  J.  prakt.  Chem.  1899,  60,  364. 


252  CHAIN  AND  RING  FORMATION 

suggested  that  in  the  preparation  of  cinnamic  acid,  the  benzylidene 
diacetate,  which  is  produced  by  the  interaction  of  benzaldehyde  and 
acetic  anhydride,  and  which  is  known  to  decompose  into  cinnamic 
acid,  may  undergo  isomeric  change  and  then  lose  a  molecule  of  acetic 
acid. 

/OCOCHg  xO.CO.CH 

- 


X)COCH3  XCH2.COOH 

-»  C6H5.CH:CH.COOH  +  C2H402 

Perkin's  theory  of  the  process  bears  a  strong  resemblance  to  that 
recently  suggested  by  Claisen1  toexplain  the  acetoacetic  ester  synthesis. 
These  conflicting  results  are  difficult  to  adjust,  and  the  question  of 
the  course  of  the  reaction  must  be  left  for  the  present  undecided. 

Thorpe's  Reaction.  A  veiy  different  reaction  from  the  foregoing 
has  already  been  referred  to  in  the  introduction  to  this  chapter,  namely 
one  involving  isomeric  change  between  molecules  or  parts  of  a  mole- 
cule, a  reaction  which  has  been  introduced  and  elaborated  by  Thorpe 
and  his  co-workers.2  To  take  a  simple  case,  sodium  cyanacetic  ester 
combines  with  cyanacetic  ester  as  follows : 

C2H5OOC.CH2 

|      +  HCNa(CN) .  COOC2H5 

CN 

C2H5OOC.CH2 

C( :  NH) .  CNa(CN) .  COOC2H5 

A  similar  reaction  takes  place  when  a  cyanogen  group  is  rendered 
acidic  by  attachment  to  a  benzene  nucleus  : 

CGH5CN  +  H2C(CN) .  COOC2H5  =  C6H5C(NH) .  CH(CN) .  COOC,H5 
Benzyl  cyanide,  which  may  be  substituted  for  the  molecule  of  cyan- 
acetic  ester,  condenses  in  presence  of  sodium  ethoxide  in  a  similar 
fashion : 

C6H5CN  +  H2C(CN)C6H5  =  CCH5C(NH)CH(CN)C6H5 
These   reactions  serve  admirably   for    preparing   cyclic   structures, 
provided   two   cyanogen   groups   are   suitably   situated  within   the 
molecule. 

On  heating  an  alcoholic  solution  of  o-xylylene  cyanide  with  a 
little  sodium  ethoxide,  ring  formation  at  once  takes  place,  with  the 
formation  of  a  cyclopentane  ring : 

1  Per.,  1903,  36,  3674  ;  1905,  38,  709. 

2  Trans.  Clem.  Soc.,  1904,  85,  1726;  1906,  89,  1906  ;  1907,  01,  578,  1004  ;  19CS, 
9U,  165. 


THORPE'S  REACTION  253 

H2.CN         •  /CH.>v 

C,II4<  -*     C.H/       ->C:NH 


and  aS-dicyanovaleric  ester  (tetramethylene  cyanide  not  being  avail- 
able for  the  purpose)  gave  a  corresponding  compound. 

CH2  .  CH2  .  CN  CH2  .  CH(CN) 


CH2.CH.CN  CH2.CH 

COOC2H5  COOC2H5 

These  compounds  are  readily  hydrolysed  by  heathig  with  dilute 
sulphuric  acid,  the  C  :  NH  group  exchanging  NH  for  oxygen.  In  the 
last  example  hydrolysis  converts  the  cyanogen  group  into  carboxyl, 
which  along  with  that  of  the  ester  group  is  removed  and  cyclopen- 
tanone  is  formed. 

CH2  .  CH(COOH)  CH2  .  CH2 


CH*  .  CH(COOH)  CH2  .  CH2 

Naphthalene  derivatives  have  also  been  obtained  by  condensing 
benzyl  cyanide  with  sodium  cyanacetic  ester  and  then  heating  the 
product. 

CH2  CH 

:  NH 


I/IC  :  NH  P  : 

I    J     LH.COOC.HS     '  I    I  x«cH. 


cooc2H5 

CN  C:NH 

With    concentrated   sulphuric   acid  the   latter  passes  into  the   di- 
amino-compound  and,  finally,  on  hydrolysis  of  the  ester  group  and 
heating,  into  naphthylene-diamine.1 
CH 


!H.COOC2H5 
C.NH2 

REFERENCES. 

Die  synthetischen  Darstellungsmethoden  der  Kohlenstof-Verbindungen,  by  K.  Elbs. 
Barth,  Leipzig,  1889. 

Syn'Jictische  Methoden  der  organise/ten  Cbcmie,  by  T.  Posner.     Leipzig,  1903. 

1  Tfans.  Clxin.  Soc.,  1907,  91,  1C87  ;  1909,  95,  2C1. 


254  CHAIN  AND  RING  FORMATION 

ArbeUsmefhoden  Jtir  organisch-chemische  Laboratorien,  3rd  ed.,  by  Lassar-Colm. 
Voss,  Hamburg,  1902. 

Die  Methoden  der  oryanischen  Chemie,  vol.  ii,  part  i,  by  Th.  Weyl.  Thiome, 
Leipzig,  1911. 

II.  UNION  OP  CARBON  AND  NITROGEN 

Carbon-Nitrogen  Chain  Formation.  In  order  to  understand  the 
processes  underlying  ring  formation  in  heterocyclic  compounds  con- 
taining nitrogen,  it  is  desirable  to  consider  first  the  various  reactions 
which  determine  the  simple  linking  of  carbon  and  nitrogen.  Com- 
pared with  methods  of  union  of  carbon  and  carbon  the  number  is 
much  more  restricted  and  the  attachment  generally  less  stable. 

Substitution  Methods.  It  is  not  always  easy  to  differentiate 
between  reactions  effected  by  replacement  and  by  addition. 

1.  For  example,  the  action  of  alkyl  iodide  on  an  amino  or  imino 
group,  which  appears  to  be  one  of  simple  substitution,  cannot  be 
explained  in  this  way.  Nitrogen,  being  more  electronegative  than 
carbon,  should  attach  hydrogen  more  firmly,  nevertheless  alkyl 
halides  have  no  action  on  paraffins.  But  if  we  suppose  an  additive 
compound  to  be  first  formed  and  hydrogen  iodide  then  removed,  the 
process  becomes  more  intelligible. 

CH3 

— NH2-fCH3I  -»  — NH2  -»  —  NHCH3  + HI 


Other  reactions  leading  to  the  union  of  carbon  and  nitrogen  by 
replacement  are  : 

2.  The  action  of  acid  chlorides  on  amino-  and  imino-compounds, 
giving  amides. 

3.  The  action  of  ammonia  and  amino-compounds  on  esters  with 
elimination  of  alcohol,  and,  in  some  cases,  on  acids  with  separation  of 
wrater,  giving  amides. 

4.  The  action   of  amino-   or  imino-compounds   on    unsaturaied 
alcohols  (tautomeric  diketones  and  ketonic  esters). 

>C= C(OH)  +  HN<     -*     >c=c— N<-+  H20 

5.  The  action  of  aldehydes  and  ketones  on  amino-compounds  and 
hydrazines,  giving  unsaturated  compounds  by  removal  of  water. 

>CO  +  H2N—    ->    >C:N— +  H2O 

6.  The  action  of  nitroso-compounds  on  the  CH2  group  suitably 
situated. 

>CHa-fON—    -^    >C:N— +  H.O 


ADDITIVE   METHODS  255 

Additive  Methods.     Among  the  methods  are : 

1.  Reactions  by  direct  addition  of  unsaturated  compounds,  as  in  the 
formation  of  pyrazole  from  acetylene  and  diazomethane, 

CH  CH2  CH=CHX 

III        +      /\        =       I  >NH 

CH  N=H  CH— N  / 

Acetylene.     Diazomethane.  Pyrazole. 

2.  Reactions  involving  intermolecular  isomeric   change   of   the 
following  general  form  : 

CN  =  HN.C:NH 


This  reaction  has  been  frequently  applied  in  ring  formation,  as  in 
the  case  of  amino-indole,  which  is  prepared  from  o-amino  benzyl 
cyanide  in  presence  of  alkalis  ; l 

CH,  CH 

C.NH2 

[H 

3.  Another  reaction  of  the  same  type   is   that  of  the   union   of 
a  saturated  amino-compound  with  an  unsaturated  acidic  group. 

-NH2-f>C:C<  =  NH.C— CH 
Piperidine  combines  with  fumaric  and  other  unsaturated  esters.2 

HC .  COOCoH5      C3H10N .  HC .  COOC2H5 
C5H10NH+     ||  =  | 

HC .  COOC2H5  H2C .  COOC2H5 

4.  Intramolecular  change  effected  by  Beckmann's  reaction  (Part  II, 
p.  366),  is  one  which  has  also  been  used  in  ring  formation.3     The 
oxime  of  cyclopentanone  gives  piperidone, 

CH2— CH2  CH2-CH2— CO 

\C:NOH     -» 
CH2-CH2  CH2— CH2— NH 

Cyclopentanone  oxime.  Piperidone. 

Stability  of  Carbon-Nitrogen  Chain  Formation.  The  attach- 
ment of  carbon  and  nitrogen  such  as  occurs  in  the  case  of  the  amines 
and  amino-compounds,  in  which  both  atoms  are  saturated  with 

1  Pschorr  and  Hoppe,  Ber.,  1910,  43,  584. 

2  Ruhemann,  Trans.  Chem.  Soc.,  1898,  73,  723. 

s  Kipping,  Proc.  Ctem.  Soc.,  1893,  9,  240;  Wallach,  Annalen,  1900,  312,  171  : 
Bamberger,  Ber.,  1894,  27,  1954,  2795. 


256  CHAIN  AND   RING   FORMATION 

hydrogen  or  hydrocarbon  radicals  (forming  the  group  CH2  .  NR2)  is 
about  as  stable  as  the  carbon-carbon  union  in  paraffins.  The  most 
drastic  treatment  will  rarely  sever  the  carbon  from  the  nitrogen. 
This  condition  is,  however,  greatly  modified  if  the  hydrogen  of  the 
CH2  group  is  replaced  by  oxygen.  The  basic  character  of  the 
nitrogen  is  not  only  greatly  weakened,  but  the  new  group,  CO  .  NR2  , 
which  is  characteristic  of  the  class  of  amides,  is  readily  hydrolysed  by 
alkalis,  and  the  carbon  and  nitrogen  separated,  the  former  ascarboxyl 
and  the  latter  as  ammonia  or  amine.  This  effect  of  oxygen  in 
weakening  the  attachment  of  the  neighbouring  atom  seems  to  bo 
common  to  all  chain  and  ring  formations. 

The  union  of  unsaturated  carbon  and  nitrogen  (RC  •  N,  RN  :  C, 
R2C  :  NR)  which  occurs  in  such  compounds  as  the  cyanides,  iso- 
cyanides,  oximes,  hydrazones,  &c.,  is  likewise  readily  severed  by 
hydrolysis  with  acids.  It  may  be  convenient  here  to  draw  attention 
to  the  nature  of  the  nitrogen-nitrogen  combination  occurring  in  carbon 
compounds.  It  appears  at  first  sight  somewhat  remarkable  that  the 
union  of  nitrogen  with  itself  should  be  so  much  less  stable  than  that 
of  carbon.  Carbon,  it  is  true,  is  electrochemically  more  inert  than 
nitrogen,  which  is  the  more  electronegative  element  ;  but  it  seems 
scarcely  adequate  for  explaining  the  fact  that  a  chain  of  at  least  sixty 
carbon  atoms  may  exist  in  a  stable  condition  in  the  case  of  the 
paraffin  hexacontane,  C60H122,  whilst  the  longest  chain  of  nitrogen 
atoms  saturated  with  hydrogen  or  hydrocarbon  radicals,  so  far  pro- 
duced, contains  only  three  nitrogen  atoms.  The  substance  in  question 
was  obtained  with  great  difficulty  by  Thiele  l  by  the  reduction  of  the 
corresponding  unsaturated  triazene  compound  in  the  cold,  but  is  of 
so  unstable  a  character  that  it  decomposes  above  0°  and  could  not  be 
isolated  in  the  pure  state. 
NH 


V 

>C.NH.N:N.CONH2  ->  C  .  NH  .  NH  .  NH  .  CONH 

^ 


Triazene  compound.  Triazane  compound. 

Unsaturated  nitrogen  chains  are  much  more  stable  and  maybe  obtained 
with  comparative  ease,  containing  two,  three,  four,  and  five  atoms  of 
nitrogen,  as  in  the  diazo-  and  the  diazoamino-compounds,  R  .  N=N  . 
NH.R,  the  diazohydrazides,  RN=N.  N(R)  .  NH2,  the  tetrazones 
R2N  .  N=N  .  NR2,  and  the  bis-diazoamino-compounds,  obtained  by 
combining  two  molecules  of  a  diazo-compound  with  one  molecule  of 
ammonia  or  amine,  R  .  N—  N  .  NH  .  N—  N  .  R.  None  are,  however, 
very  stable,  and  all  readily  decompose  with  acids  or  when  heated, 
1  Annaltn,  1899,  305,  84. 


CARBON-NITROGEN  CHAIN  FORMATION  257 

giving  off  nitrogen,  often  with  explosive  violence.  The  longest 
unsaturated  chain  So  far  obtained  is  tetraphenyloctazene,  and  contains 
eight  nitrogen  atoms.1 

C6H5N  :  N .  N(C6H5) .  N  :  N  .  N(C6H5)N  :  N .  C6H5 

Tetraphenyloctazene. 

Only  a  very  minute  quantity  was  prepared,  as  it  rapidly  suffers 
decomposition. 

King  Formation.  Ring  formation  seems  to  be  governed  by  the 
same  general  principle  which  underlies  that  of  the  carbo-cyclic  com- 
pounds, that  is,  the  stability  increases  up  to  five  and  six-atom  rings 
and  is  not  seriously  affected  in  such  cases  by  the  replacement  of  carbon 
by  nitrogen  at  least  to  the  extent  of  four  atoms  ;  in  fact,  unsaturated 
ring  systems  of  five  atoms  appear  to  increase  in  stability  with  increase 
in  the  number  of  nitrogen  atoms  up  to  the  above  number.  In  con- 
sidering the  stability  of  ring  structures  containing  one  nitrogen  atom 
it  is  interesting  to  follow  the  formation  of  the  latter  by  the  general 
method  of  heating  the  hydrochloride  of  the  diamine,  when  ammonium 
chloride  is  removed  and  a  saturated  ring  system  produced.  Tetra- 
methylene-diamine  hydrochloride,  for  example,  gives  pyrrolidine. 

CH2 .  CH2 .  NH2 .  HC1      CH2— CH2 


I 


.  CH2 .  NH2 .  HC1      CH2-CH2 

The  same  reaction  takes  place  with  pentamethylene-diamine,  giving 
a  six-atom  ring  ;  but  the  higher  homologues  give  other  products.  The 
compound  obtained  by  heating  octomethylene-diamine  and  which  was 
formerly  supposed  to  yield  a  nine-atom  ring  has  been  shown  to  be 
butyl  pyrrolidine. 

CH2— CH2 

CH3 .  CH2 .  CH2 .  CH2 .  CH     CH2 

NH 

Although  the  four-ring  system,  trimethylene-imine,  is  produced  by 
heating  the  hydrochloride  of  trimethylene-diamine,  its  formation  is 
accompanied  by  a  variety  of  complex  by-products,  whilst  the  corre- 
sponding ethylene-imine  cannot  be  prepared  by  this  method.  Thus 
the  five  and  six-ring  systems  appear  to  be  the  most  stable. 

Trimethylene-imine  is  probably  produced  by  heating  bromethyl- 
amine  with  potash,  when  hydrogen  bromide  is  removedand  a  compound, 

1  Wohl  and  Schiff,  Ber.,  1900,  33,  2745. 
PT.  I  S 


258  CHAIN  AND  RING   FORMATION 

C2H5N,  formed  ;  nevertheless  the  substance  behaves  in  many  respects 
like  an  unsaturated  compound,  uniting  with  hydrogen  chloride,  giving 
chlorethylamine,  and  with  sulphurous  acid  to  form  taurine.  On  the 
other  hand,  it  may  be  argued  that  ethylene  oxide  shows  the  same 
tendency  to  pass  into  an  open-chain  structure  by  addition,  so  that 
at  present  no  definite  conclusion  can  be  reached.  Marckwald l  is 
inclined  to  adopt  the  ring  formula  on  the  ground  that  the  product 
of  the  action  of  benzenesulphonic  chloride  is  insoluble  in  alkalis  and 
consequently  the  original  nitrogen  was  present  as  an  imino  group. 

A  trimethylene-imine  ring  can  be  prepared  from  trimethyleno 
bromide  and  toluene  sulphonamide. 

BrCH2  CH2 

CH3 .  C6H4S02NH2  +       \CH2  =  CH3 .  C6H4S02N/\CH2  +  2HBr 
BrCH2  CH2 

From  this,  the  toluene  sulphonyl  group  may  be  removed  by  reduction, 
leaving  trimethylene-imine  in  the  form  of  a  liquid  boiling  at  63° 
with  a  strong  ammoniacal  smell.  Like  ethylene-imine  it  is  very 
unstable  and  readily  passes  into  an  open  chain  by  the  action  of  acids. 

Carbon-Nitrogen  Ring  Formation.  The  various  types  of  re- 
actions summarized  in  the  foregoing  paragraphs  will  explain  the 
greater  number  of  processes  applied  to  the  formation  of  heterocyclio 
ring  systems,  containing  nitrogen.  As  the  synthesis  of  six-atom 
rings  containing  one  nitrogen  atom  will  be  discussed  later  under 
alkaloids,  we  shall  illustrate  the  above  reactions  by  reference  to 
five  atom  rings  containing  from  one  to  four  atoms  of  nitrogen.2 
An  attempt  to  extend  the  study  to  other  ring  systems  would  occupy 
more  space  than  the  theoretical  value  derived  from  such  a  compre- 
hensive treatment  of  the  subject  would  warrant. 

The  system  of  nomenclature  applied  to  these  five-atom  ring  struc- 
tures is  to  indicate  the  number  and  position  of  the  nitrogen  atoms 
in  the  first  part  of  the  name,  to  which  the  suffix  -ole  is  then  attached. 

3'HC-CH3  HC-CH  HC— CH 

II     II  II     II  II      II 

2'HC    CH2  HC    N  N    N 

\/  \7  V 

1NH  NH  CH 

Pyrrole.  1 .  2  Diazole.  2  .  2'  Diazole. 

1  Ber.,  1899,  32,  2086. 

2  An  account  of  5-membered  carbon-nitrogen  rings  is  given  by  Ciamician. 
Ber.,  1904,  37,  4200. 


\ 

N 


CARBON-NITROGEN  RING  FORMATION  259 

HC-CH  N—  CH  HC—  N  N—  N  HC—  N 

I!    il  II     II  II    II  II    II  II     II 

N    N  HC    N  HC    N          HC     CH  N     N 

\/  \/        \/         v 

H  NH  NH  NH  NH 

1.2.2'  1.2.3'  1.2.3  1.3.3'  Tetrazole. 

Triazole.  Triazole.  Triazole.  Triazole. 

The  various  reduction  products  are  indicated  by  adding  the  termi- 
nation -ine  to  the  name  if  two  hydrogen  atoms  are  added,  and  if 
four  hydrogen  atoms  are  introduced  the  termination  -idine  is  added, 
whilst  the  presence  of  a  ketone  group  in  the  ring  is  indicated  by  the 
suffix  -one,  &c.  Thus  pyrrole  forms  on  reduction  the  compounds 
pyrroline  and  pyrrolidine,  and  if,  in  the  last,  two  hydrogen  atoms  are 
replaced  by  oxygen,  the  product  is  called  pyrrolidone. 

H2C—  CH  H.C-CH2  H2C-CO 

I      II  II  II 

H2C    CH  H2C    CH2  H2C    CH2 

NH  NH  NH 

Fyrrolinc.  Pyrrolidinc.  3.  Pyrrolidono. 

The  parent  substances  themselves  exhibit  for  the  most  part  weak 
basic  characters,  due  no  doubt  to  the  acidic  character  of  the  unsatu- 
rated  nucleus,  for  the  basicity  is  immediately  enhanced  on  reduction. 
Whereas  pyrrole  is  weakly  basic  as  well  as  weakly  acidic  (the 
hydrogen  of  the  NH  group  is  replaceable  by  alkali  metals  as  in 
phenol),  pyrroline  has  all  the  properties  of  a  secondary  base  and 
pyrrolidine  is  still  more  strongly  basic,  with  an  ammoniacal  smell 
resembling  piperidine. 

Among  the  methods  used  for  obtaining  members  of  the  pyrrole 
series  are  : 

1.  The  action  of  ammonia  on  1  .  4  diketones  which  follows  the 
course  R  R  R 


-I. 


CH2— CO  CH  =  C .  OH  CH  =  C .  OH 


CH  =  C. 


CHa— CO  CH  =  C .  OH  CH  =  C .  NH, 


=    X 

-»     |  >NH  +  H,0 

CH  =  CK 


1 


that  is,  the  diketone  isomerises  to  the  tautomeric  form. 

s  2 


260  CHAIN  AND  KING  FORMATION 

2.  The  action  of  heat  on  glutamic  acid, 


, 
CH2—  CH  CH2—  CH  .  COOH 

\NH         -»  \NH 


2 
CH2—  COOH  CH2—  CO 

3.  Succinimide,  derived  from  succinic  anhydride  by  the  action  of 
ammonia,  may  be  regarded  as  a  pyrrolidone,  for  it  may  be  converted 
into  pyrrolidine  on  reduction  with  sodium  in  alcoholic  solution. 

4.  Pyrrolidine  is   also  formed   by  heating  the   hydrochloride  of 
tetramethylene  diamine,  or  by  removing  hydrogen   chloride  from 
5-chlorobutylamine. 

CH2.CH2.NII2  CH2.CH2V 

|  -»       |  )NH  +  HC1 

CH2.CH2.C1  CH2.CH/ 

5.  Pyrrole  itself  is  prepared  by  heating  ammonium  mucate,  which 
is  probably  converted  into  the  intermediate  form,  and  then  reacts 
with  ammonia,  at  the  same  time  losing  carbon  dioxide  and  water.1 

HC—  CH  HC—  CH 


SH,  ||      ||      + 

HO.C    C.OH  -*  HC    CH 

I      I  \/ 

HO.OC    CO. OH  NH 


It  should  be  pointed  out  that  the  stability  of  the  ring  is  greatly 
weakened  by  attaching  oxygen  to  the  carbon  members  of  the 
ring.  Succinimide,  for  example,  is  readily  hydrolysed  and  the  ring 
broken.  But  the  non- oxygenated  derivatives  are  comparatively 
resistant  to  ring  cleavage.  It  can,  however,  be  effected  if  the  open 
chain  is  prevented  from  closing  by  the  presence  of  a  reagent  with 
which  the  compound  can  combine.  Thus,  the  pyrrole  ring  can  be 
broken  by  alkalis  in  presence  of  hydroxylamine.  Water  is  taken 
up,  ammonia  expelled,  and  the  dialdehyde,  thus  produced,  unites  with 
the  reagent, 

HC— CH  H2C— CH2  H2C-CH2 

||      ||     +  2H20  =          |      |         +  NH3->  || 

HC    CH  OHC    CHO  HON:CHCH:NOH 


Pyrazole  and  its  homologues  have  weak,  but  distinctly  basic  pro- 
perties, forming  salts  and  double  salts  and  behaving  as  secondary 
bases. 

1  Ciamician,  Ber.t  1904,  37,  4205. 


CARBON-NITROGEN  RING   FORMATION  261 

Its  formation,  and  that  of  its  numerous  derivatives,  may  be 
accomplished  by  an  extraordinary  variety  of  synthetic  methods. 

1.  A  process  of  addition  is  illustrated  by  a  method  corresponding 
to  the  formation  of  pyrazole  from  acetylene  and  diazomethane 
already  referred  to  (p.  204).  Other  acetylene  and  olefine  derivatives 
may  be  substituted  for  acetylene,  and  diazoacetic  ester  for  diazo- 
methane. Fumaric  ester  unites  with  diazoacetic  ester  thus : 

CH .  COOC2H5  HC .  COOC2H5    C2H,OOC .  C  —  C .  COOC2H5 
N=N  HC.COOC2H5~  N    C.COOC2H5 

YH 

Where  open-chain  compounds  combine  by  substitution,  it  is 
requisite  that  union  takes  place  at  two  points.  Combination,  with 
simultaneous  elimination  of  halogen  acid  and  water  or  alcohol,  is 
illustrated  by  the  following: 

Epichlorhydrin  and  hydrazine  combine  in  presence  of  zinc  chloride, 
and  at  the  same  time  hydrogen  is  eliminated  and  pyrazole  is  formed. 

CH2-  CH .  CH2C1         HO  .  CH— CH— CH2C1         HC=CH— CH2 
\/                      ->                   +                     -*       | 
O  H2N NH2  HN NH 

HC CH 


I 


CH 

NH 

/2-Chlorobutyric  acid  and  phenylhydrazine  give  2-phenyl,  3- methyl, 
1-pyrazolidone,  which,  on  oxidation,  gives  the  corresponding  pyra- 
zolone : 
CH3— CHC1— CH2  CH3.CH— CH2  CH3.C=CH 

I  ~>      -          I         I  II 

COOH  C6H5.N       CO  CCH5.N    CO 


C0H5.NH— NH2  NH 

Phenylmethyl  Phenylmethyl 

pyrazolidone.  pyrazolone. 

/Modopropionic   ester   and   phenylhydrazine    react  in   a  similar 
way. 

CH2I-CH2  H2C-CH2 

NH2      COOC2H-     -»      HN    CO  +C2HOH  +  HI 
\  V 

"WTT     C*   IT  XT     C*  TT 

JM±l.O6tl5  JN  .  O0115 

Substitution  and  intramolecular  isomeric  change  occuiTing  together 


262  CHAIN  AND   RING   FORMATION 

are  illustrated  by  the  union  of  acrolein  and  acrylic  acid  with  hydrazine 
and  its  derivatives : 

HC— CHO  H2C— CH  HC— CO.  OH  H2C— CO 

H2C    NH2  H2C    N  '  H2C        NH2  H,,C    NH 


H2N  NH  H2N  NH 

But  the  most  prolific  source  of  pyrazole  compounds  is  that 
furnished  by  the  method  of  Knorr,  namely,  the  interaction  of  1.3 
diketones  or  ketonic  esters  with  hydrazines.  The  most  familiar 
example  is  that  of  acetoacetic  ester  and  phenylhydrazine  : 

CH3 .  CO .  CH2  CH3 .  C— CH2 

NH2    CO.OC2H5  N    CO 

NH  N 

i  i 

If  a  1 .  3  diketone  is  used  in  place  of  a  ketonic  ester  two  molecules 
of  water  are  removed  and  no  oxygen  appears  in  the  product.  Acetyl 
acetone  and  hydrazine  react  thus : 

CH3 .  CO .  CH2  CH3 .  CO .  CH  CH3 .  C— CH 

NH2      CO.CH3  NH2    COH.CH3  N    C.CH3 

NH2  NH2  NH      * 

2 .  2'  diazoles  (glyoxalines,  iminazoles)  are  stronger  bases  than 
the  foregoing  and  form  stable  salts  with  acids.  The  common  method 
for  obtaining  them  is  by  the  combined  action  of  ammonia  or  amine 
and  aldehyde  on  an  ortho  diketone : 

R— CO 

R— CO  R-C-NH/ 

H 

Another  method  is  by  the  removal  of  a  molecule  of  acid  from 
a  diacyl  diamine : 

CH9— NH .  COC,.HS        CH2— N^ 


CH2—  NH  .  COC6H5        CH2—  NH 


I 

CH— 


Finally,  the  linking  of  a  molecule  of  urea  with  chloracetal  and 
removal  of  alcohol  gives  a  diazolone. 


CARBON-NITROGEN   RING   FORMATION  2G3 


CH(OC2H5)3      NII2 

+    \co  -*•  \CO  +  2C2H5OH 

CH2C1  NH2  CH2— NH 


CH— NH 

^>CO 
JH— NH 

The  1.2.2'  triazoles  (osotriazoles)  are  mostly  oils  with  an  alka- 
loidal  smell,  and  weak  basic  characters.  At  the  same  time  they  are 
remarkably  stable  towards  oxidising  agents,  the  side-chains  being  oxi- 
dised like  those  of  benzene  derivatives  to  carboxyl.  Nitro-compounds 
and  sulphonic  acids  can  also  be  obtained  by  nitration  and  sulphonation 
in  the  ordinary  way,  whereas,  in  the  case  of  pyrrole  and  pyrazole 
derivatives,  special  methods  are  requisite.1  v.  Pechmann  was  the 
first  to  prepare  them  by  a  reaction  which  illustrates  the  greater 
stability  of  the  five-carbon  over  that  of  the  six-carbon  ring.  When  an 
osazone  is  oxidised  it  is  converted  into  a  tetrazone,  which,  by  the 
action  of  dilute  mineral  acids,  loses  one  nitrogen  group  as  primary 
amine. 

R .  C  :  N  .  NHC6II5  R .  C=N— N— C6H5 

R .  C  :  N .  NHC6H5  R .  C=N— N-  C6H5 

H20  RC=NV 


RC=N/ 

The  free  oxygen,  which  is  liberated,  acts  upon  and  resinifies 
a  portion  of  the  material. 

A  second  method  consists  in  removing,  by  means  of  acetic  an- 
hydride or  dilute  alkali,  the  elements  of  water  from  the  hydrazoxime 
of  a  1.2  diketone, 


R  .  C=N  .  NHCfiH5  R  .  C=NV 


-»  |  NCCH5 

R.C=N 


R.C^N.OH 

The  1.2.3'  triazoles  contain  the  atoms  of  the  ring  in  the  order 
—  C  —  N  —  C  —  N  —  N  —  so  that  such  combinations  as  the  following 
might  be  anticipated  : 

1.     —CO    NH2.CO  2.    —  CO.NH.COOC2H5 

I     +  I 

OH    H2N.NH  +  NH2.NH— 

1  Indol-  und  Pyrrolgruppe,  by  Angeli.    Ahrena'  Vortrage,  1912,  17,  312. 


264  CHAIN  AND  RING  FORMATION 

8.  —CO .  NH2  +  CO       4.  —CO  .  NH-C        5.  II.N— C 

I  II  II 

H2N— NH  H2N— N  — OC.HN— N 

All  these  processes  can  be  applied  in  one  form  or  another,  and  ono 

ample  will  be  given  of  each. 

1.  Formic  acid  combines  with  phenylsemicarbazide : 

H,N— CO  N-CO 

I  ->  II       I 

H— CO       NH  HC     NH 


NH  .  a: 


OH  NH  .  CCH5  NCGH5 

2.  Phenylhydrazine  reacts  with  acetylurethane  : 

CH3 .  CO— NH  CH3 .  C-  NH 

H2N    COOC2H5  N    CO 

NH.CCH5  N.CCH5 

3.  Formamide  and  formylhydrazide  give  triazole : 

NH2    OCH  N-CH 

I       +      I  ->         II      II    +  2H20 

HCO         NH  HC     N 

NH2  NH 

4.  The  fourth  and  fifth  reactions  are  illustrated  by  intramolecular 
combination  as  follows : 

HN-C .  CO .  CII3  N— C .  COCH3 


,CON 


CH.CON  CH3.C    N 

IIN.C6H5  N.CGII5 

5.  Formylthiosemicarbazide  gives,  on   heating,  mercaptotriazole, 
which,  on  oxidation  with  hydrogen  peroxide,  loses  sulphur: 

H,N— C .  SH  N— C .  SH  N— CH 

II  ->         II      II  ->          II      II 

HCO  N  HC    N  HC    N 


NH  NH  NH 

An  interesting  example  of  intermolecular  isomeric  change  is  that 
of  the  action  of  phenylcyanide  on  phenylhydrazine,  which  occurs  in 
several  phases : 


CARBON-NITROGEN   RING   FORMATION  265 

HN  +  CN.C6H5 
C6H-CN  +  NH2 .  NH .  C6H3  =  CGH5 .  C    NH2 


NCCH5 
HN  H2N.C.CCH5  N— C.C6H5 

->    C6H5.C  N  -*>    C6H5C     N 


NCGH5 

1.2.3  triazoles  belong  mainly  to  the  aromatic  series  in  the  form 
of  azimidobenzene  and  its  derivatives : 


FH 

Azimidobenzene. 

and  few  members  of  the  single-ring  system,  obtained  by  direct 
synthesis,  are  known.  Like  the  foregoing,  they  are  very  stable,  and 
may  be  obtained  indirectly  by  oxidising  and  removing  the  benzene 
nucleus.  Thus,  azimidobenzene  on  oxidation  gives  the  triazole  dicar- 
boxylic  acid,  from  which  carbon  dioxide  may  be  removed : 

/\ N  HOOC .  C— N  HC— N 

I       I    -*     HOOC   H      ~*     H<H 

\      A      /N  xiUUO .  U      .W  HU      £\ 

X/  \/_  \   /  \    / 

NH 


As  azimidobenzene  and  its  derivatives  are  readily  prepared  by 
a  variety  of  methods,  the  formation  of  single-ring  compounds  affords 
no  difficulty.  The  union  of  acetylene  dicarboxylic  ester  with  diazo- 
benzolimide  is  an  interesting  modification  of  the  pyrazole  synthesis 
described  on  p.  204. 

N=N  C .  COOC2H5  N— C .  COOC2H5 

NC.H,        C.COOC2H5  N    C.COOC2H5 

NCtiH5 

Diazobenzolimide  also  condenses  with  ketones,  1 . 3  diketones,  and 
ketonic  esters.1 


N=N  — CH2 

,H5  CO.R  HN.C6H5  N.C6H, 

1  Dimroth,  Bcr.,  1906,  39,  3920. 


266  CHAIN  AND   RING   FORMATION 

Diazoacetamide,  when  warmed  with  alkali,  is  converted  into  tri- 
azolone  : 

CH—  CO  N—  CH2 

N=  N    NH  N    CO 


The  1  .  S  .  3'  triazoles,  the  fourth  group  of  isomers,  may  be  prepared 
from  phenylthiosemicarbazide,  C6H5NH  .  CS  .  NH  .  NH2.  On  treat- 
ment with  an  acid  chloride  (benzoyl  or  acetyl  chloride),  the  change 
occurs  as  follows  : 

N—  Nil  N—  N  N—  N 

I!     I  I!     II  II     II 

HS  .  C  OC  .  CGH5      -»     HS  .  C     C  .  CGH5      —  >      HC     C  .  CCH5 
NH.C6H5  N.C6H5  N.CGH5 

The  sulphur  can  then  be  removed  by  oxidation. 

Diphenylthiosemicarbazide  and  carbonyl  chloride  can  also  be  con- 
verted into  a  triazole  derivative  : 

N-NHC6H5  N-N  .  CCH5 

IIS.cl         +  C12CO      =      HS.dl      JCO          +  2HC1 
NHC6H5  NCCH5 

A  reaction,  which  illustrates  the  greater  stability  of  a  five  atom 
compared  with  a  six-atom  ring,  is  the  conversion  of  bis-diazoacetic  acid 
by  treatment  with  strong  caustic  potash  into  a  triazole  derivative  : 

N__N  N_N 

C02H.C<  >C.C02H    ->  ||     || 

\H-NH  C02H.C^C.C02H 

N.NH2 
Tetrazole  should  be  represented  by  two  isomeric  compounds. 

N-CH  N—  N 

II     II  II      II 

N     N  HC     N 


NH  NH 

1 .  2  .  2' .  3  Tetrazole.  1.2.3.3'  Tetrazole. 

As  a  matter  of  experience,  only  one  (the  first  of  the  above)  is 
known.  It  is,  in  short,  a  case  similar  to  that  of  methylpyrazole 
(Part  II,  p.  328),  or  of  the  single  ortho  compound  in  the  benzene 
series. 


CARBON  NITROGEN   RING  FORMATION  267 

The  tetrazoles  are  remarkably  stable  substances.  Oxidation  will 
destroy  a  side-chain,  but  leaves  the  tetrazole  nucleus  intact.  Moreover, 
tetrazoles  are  characterised  by  acidic  properties,  in  which  the 
hydrogen  of  the  NH  group  is  replaceable  by  metals. 

There  are  numerous  methods  by  which  the  tetrazoles  have  been 
prepared,  among  which  the  following  are  included  : 

Bladin,  who  prepared  cyanamidrazone  by  the  action  of  cyanogen 
on  phenylhydrazine,  obtained  the  first  tetrazole  compound  by  acting 
on  the  former  with  nitrous  acid  : 

(CX)C—  NH,  (CN)C—  N 

I'T   -*       111 

\    i 

NH    OH 


Hydrolysis  converts  the  cyanogen  group  into  carboxyl,  and  oxida- 
tion has  the  same  effect  on  the  phenyl  group.  On  splitting  off 
carbon  dioxide,  tetrazole  itself  is  formed  as  a  solid,  melting  at  156°. 
Benzylidene  amidine  is  converted  by  nitrous  acid  into  the  diazo- 
nitrosamine,  which  passes  on  reduction  into  3-phenyl  tetrazole  : 

C0H5C—  NH2  C0H5  .  C—  N  C0H5C  -  N 

II  —  I      II  —  II      II 

NH  N     NOH  N    N 


NO 


NH 

Hydrazides  behave  like  the  amidines  with  nitrous  acid  : 

C6H5C—  NH9  CCH5  .  C—  N 

II  O  ||      || 

N  N        ->  N    N     +  2H20 


NH2    OH  NH 

Aminoguanidine,  inasmuch  as  it  resembles  a  hydrazide,  undergoes 
a  similar  change,  and  gives  aminotetrazole. 

The  action  of  nitrous  acid  on  the  nitrate  of  the  base  gives  a  diazo- 
compound,  which  changes  into  the  ring  compound.1 

HN03 .  NH2 .  C— NH          HNO3 .  NH2 .  C N  NH2 .  C— NH 

Unr       '^Ar  'u 


1  Thiele,  Annalen,  1892,  270,  1  ;  Hantzsch  and  Vogt,  Annalen,  1901,  314,  339. 


268  CHAIN  AND  RING   FORMATION 

In  the  same  way  phenylthiosemicarbazide  may  be.  used,  and  the 
sulphur  subsequently  removed  by  oxidation  : 

HN— NH2        O  N— N  N— N 

SO          HO— N      -*      HS.C     N        ->    HO.C    N 

NH.CCH-  N.C6H5  N.C6II5 

Hydroxytetrazole   has  been   obtained   by  the   action   of  sodium 
fulminate  on  azoimide.1 

HNi\  C  N,=-,CH 

+     II 

N  .  OH  NX/N •  OH 

N 


Six  membered  rings  containing  nitrogen  are  dealt  with  under 
Alkaloids  (this  volume,  Part  III). 

REFERENCES. 

Die  heterocyklischen  Verlindungen,  by  E.  Wedekind.     Veit,  Leipzig,  1901. 
The  Organic  Chemistry  of  Nitrogen,  by  N.  V.  Sidgwick.     Clarendon  Press,  Oxford, 
1910. 

III.  UNION  OF  CARBON  AND  OXYGEN 

Carbon-Oxygen  Chain  Formation.  Chain  formation  between 
carbon  and  oxygen,  in  which  both  atoms  are  saturated  with  hydrogen, 
is  represented  by  the  alcohols  and  ethers.  In  the  latter  only  can 
the  union  be  regarded  as  a  stable  one,  and  the  stability  is  greatly 
diminished,  as  in  the  case  of  the  carbon-nitrogen  linkage,  by  replacing 
the  hydrogen  of  the  adjoining  carbon  by  oxygen.  The  esters,  and 
still  more  the  anhydrides,  thus  formed,  are  easily  hydrolysed. 

CH2— 0-CH2  CO— 0— CH2  CO— 0— CO 

ii  ii 

Ether  group  Ester  group  Anhydride  group 

(stable),  (less  stable).  (least  stable). 

Union  between  oxygen  and  oxygen  is  even  less  stable  than  between 
nitrogen  atoms,  as  seen  in  the  peroxides  and  ozonides  (p.  119),  which 
decompose  with  explosive  force.  As  only  peroxides  of  acid  radicals 
are  known,  it  is  impossible  to  say  whether  those  with  hydrocarbon 
radicals  would  exhibit  greater  stability. 

Carbon-Oxygen  Ring  Formation.  When  we  apply  these  prin- 
ciples to  ring  formation  we  find,  as  before,  that  they  are  not  the 
only  factors  in  determining  the  stability  of  the  system,  but  that  it  is 

1  Palazzo  and  Marogna,  Chem.  Soc.  Abs.,  1913,  i.  300. 


CARBON-OXYGEN  RING  FORMATION  269 

also  largely  influenced  by  the  number  of  atoms  composing  the  ring. 
Ethylene  oxide  is  a  low-boiling  liquid,  which  was  first  obtained  by 
removing  hydrogen  chloride  by  means  of  alkali  from  ethylene 
chlorhydrin  ;  but  it  is  extremely  unstable,  exhibiting  in  various 
ways  a  tendency  to  cleavage  at  the  carbon-oxygen  link,  and  to  pass 
into  an  open-chain  compound.  The  number  of  representatives 
of  four-atom  rings  containing  oxygen  in  the  ring  is  very  small. 
Trimethylene  oxide  has  been  prepared,  and  is  a  liquid  boiling  at 
50° ;  but  few  of  its  derivatives  are  known.  On  the  other  hand,  five- 
atom  rings  containing  one  atom  of  oxygen  are  comparatively  stable, 
and  comprise  a  very  large  number  of  compounds,  termed  furfurane 
derivatives.  Though  tetramethylene  oxide,  or  tetrahydrofurfurane, 
has  been  prepared,  the  furfurane  derivatives  are  for  the  most  part 
unsaturated,  furfurane,  the  parent  substance,  having  the  formula, 

HC— CH 

fe 


0 

Furfurane. 

The  scarcity  of  saturated  ring  compounds  of  this  type  would 
appear  to  indicate  that  they  are  not  readily  formed,  and  it  is 
significant  that  among  nitrogen  ring  compounds  unsaturation  has 
a  distinct  tendency  in  the  direction  of  increasing  the  stability  of 
the  system. 

There  are  various  ways  in  which  furfurane  compounds  are  obtained. 
The  oldest  method  is  to  distil  carbohydrates  with  dilute  sulphuric 
acid,  which  produces  furfuraldehyde.  The  same  compound  is  ob- 
tained by  distilling  a  pentose  with  hydrochloric  acid  (Part  III,  p.  18). 

HC—  CH 


HiHC    CH;OHCHO          -*          HC     C.CHO 


v 


Pentose.  Furfuraldehyde. 

It  is  a  colourless  liquid  with  an  empyreumatic  smell,  and  boils  at 
162\  It  has  all  the  characteristic  properties  of  an  aromatic  aldehyde, 
yielding  an  acid,  pyromucic  acid,  on  oxidation,  and  an  alcohol, 
furfuryl  alcohol,  on  reduction.  The  former,  on  distillation  with  lime 
or  baryta,  yields  furfurane. 


270                   CHAIN  AND  RING  FORMATION 

HC— CH  HC— CH 

II    II  -*        II    II    + 

HC    C.COOII  HC    CH 


O  O 

Pyromucic  acid.  Furfurane. 

Pyromucic  acid  is  also  obtained,  as  its  name  implies,  by  distilling 
mucic  acid  (Part  III,  p.  29). 

i  HOiHC-CH/OH;  HC— CH 

..J \    I     I  /•} !  II    II 

iHiOOCiHC    C/H;OHl.COOH    ->    HC     C.COOH 

:'~" '    \  W7t~  V 

O;H  O 

Mucic  acid.  Pyromucic  acid. 

Certain  1 .  4  diketones,  which  can  react  in  the  enol  form,  also  give 
furfurane  derivatives : 

CH2— CH2  CH CH  HC— CH 

B.'OO      CO.R  R.C  C.R  R.C    C.R 


I         I  V 

or    — 


>H     HO  O 

Thus,  acetonylacetoacetic  ester  and  diacetosuccinic  ester  give 
respectively  the  esters  of  pyrotritaric  and  carbopyrotritaric  acids : 

HC C .  COOR  HC— C .  COOR 

CH3.C        C.CH3  ->        CH3C     C.CH3 

OH  HO  O 

Acotonylacetoacetic  ester.  Pyrotritaric  ester. 

ROOC .  C C .  COOR  ROOC .  C— C .  COOR 

CH3.C         C.CH3         ->          CH3.C     C.CH3 
OH  HO  O 

Carbopyrotritaric  ester. 

Among  the  derivatives  of  tetrahydrofurfurane  containing  oxygen 
in  place  of  carbon  may  be  included  the  lactones  of  y-hydroxy  acids 
and  anhydrides  of  the  succinic  acid  series, 


CARBON-OXYGEN  RING  FORMATION 


271 


I 
OC 


CH 


V 


II 
OC    CO 

v 

o 

Succinic  anhydride. 


•y-Butyrolactone. 

both  of  which  are  easily  hydrolysed. 

A  compound  isomeric  with  succinic  anhydride  is  the  lactone  of 
y-hydroxyacetoacetic  acid  or  tetronic  acid,  which  behaves  in  many 
ways  like  a  1 .  3  diketone. 

H2C— CO 
CH, 


A.JLOV/ 

OC 


Y 


Tetronic  acid. 

As  in  the  five-atom  ring  systems,  the  commonest  and  most  stable 
representatives  of  six-atom  rings  containing  oxygen  are  unsaturated. 
Substances  such  as  pentamethylene  oxide,  S-valerolactone,  and  glutaric 
anhydride  are  known,  but  the  number  is  small,  and  they  are  readily 
converted  into  open-chain  compounds.  On  the  other  hand,  those 
derived  from  a-  and  y-pyrone  are  numerous  and  comparatively  stable. 
As  they  are  frequently  met  with  among  natural  products,  they 
possess  a  special  interest: 


II 


II 


HOI     JCH 
O 

a-Pyrono.  7-Pyrone. 

A  further  source  of  interest  lies  in  the  fact  that  by  the  action  of 
ammonia  they  readily  exchange  the  oxygen  of  the  ring  for  NH,  and 
thus  pass  into  pyridones  or  derivatives  of  pyridine. 


HO 

CO 

||CH     NH3 

J€H 

CO 

Tr 

HOI  JCH 

X 

YH 

7-Pyrone. 

7-Pyridone. 

a-Pyridone. 
Among  the  natural  sources  of  the  simpler  pyrone  compounds  is 


272  CHAIN  AND  RING  FORMATION 

opium,  which  contains  meconic  acid,  which  on  heating  passes  into 
comenic  acid  and  pyromeconic  acid : 

CO  CO 

HC/\C.OH  HC/\C.OH 


COOH  .  Cl      "1C  .  COOH  COOH  . 


Meconic  acid.  Comenic  acid. 

CO 

HC/\C.OH 


HOI     /'CH 
O 

Pyromeconic  acid. 

Another  natural  source  is  the  greater  celandine  (clielidonium  majus), 
which  contains  an  alkaloid  combined  with  chelidonic  acid  ory-pyrone 
dicarboxylic  acid.  On  heating,  it  loses  carbon  dioxide  and  forms 
comanic  acid: 

CO  CO 

HC/^CH  HC/\CH 

-> 

COOH  .  dMto .  COOH  HcJJc .  COOH 

o  o 

Chelidonic  acid.  Comanic  acid. 

Chelidonic   acid  has   been  prepared  synthetically  by  condensing 
acetone  with  oxalic  ester  by  means   of  sodium   methoxide.      Tho 
alcoholic  solution  yields,  on  boiling,  chelidonic  ester: 
CH3  ROOC  .  COOR  CH2 .  CO .  COOR 

I  I 

CO      +  -*     CO 

CH3     ROOC .  COOR      CH2 .  CO .  COOR 

CH=C(OH) .  COOR      CH=C .  COOR 

I  I    I 

->  CO  ->  CO  O 

}H=C(OH) .  COOR      CH— C .  COOR 

Coumalinic  acid  was  obtained  by  v.  Pechmann  by  warming  malic 
acid  with  strong  sulphuric  acid,  which  removes  water  and  carbon 
monoxide.  Condensation  may  be  represented  as  taking  place  by  the 
union  of  the  unstable  intermediate  product,  formylacetic  acid  or  its 
tautomeric  form. 


CARBON-OXYGEN  RING  FORMATION 
CHOH.COOH  CH.OH    HC.COOH 


273 


CH2 
COOH 

Malic  acid. 


-»     CH 


CH 
OC.OH       HO 

Formylacetic  acid. 


CH 

HG^C.COOH 

Ocl     JcH 

o 


.COOK 


Coumalinic  acid. 
a-Pyrone  carboxylic  acid. 

Dimethylcoumalinic  acid  (isodehydracetic  acid)  is  another  pyrone 
derivative,  which  is  prepared  by  the  action  of  sulphuric  acid  on 
acetoacetic  ester  and  in  other  ways : 
CH3 

C.OH 

HC       HC.COOE 
OC.OR  C.CH3 

HO 

Dehydracctic  acid  was  first  obtained  by  Geuther  from  the  residues 
from  the  preparation  and  distillation  of  acetoacetic  ester,  and  is 
formed  by  heating  acetoacetic  ester  alone  or  with  acetic  anhydride. 
Its  structure  has  been  the  subject  of  much  discussion,  and  the 
following  alternative  formulae  have  been  proposed  by  Feist  and 

c*llie:  co  co 


HC 


.CH, 


0 


H, 


CH3.CO.CH2.C,      JCO 
O 

Collie's  formula. 


Feist's  formula. 

One  of  the  most  interesting  of  the  pyrones  is  the  dimethyl  deriva- 
tive obtained  by  heating  dehydracetic  acid  under  pressure  and  then 
dehydrating  over  sulphuric  acid.  It  has  also  been  prepared  by  the 
action  of  carbonyl  chloride  on  the  copper  compound  of  acetoacetic 
ester  and  hydrolysis  of  the  resulting  ester : 

ROOC .  CH  HC .  COOR  ROOC  .  C CO C .  COOR 

li  II  -*  II  II 

CH,.CO— < 


-Cu— OC.CII, 
+  COC1, 

"CO 


CHo.C.OH     HO.C.OrL 


ROOC. 


.COOR 
.CH3 


PT.   I 


274  CHAItf  AND  KING  FOKMATION 

It  forms  well-defined  salts  with  mineral  acids,  the  latter  combining 
with  the  cyclic  oxygen  atom,  which  acts  as  a  quadrivalent  atom. 

Among  the  more  complex  of  the  pyrones  are  those  in  which  the 
pyrone  is  fused  with  a  benzene  nucleus,  in  the  form  of  benzo-  and 
dibenzo-y-pyrone  compounds,  which  may  be  regarded  as  the  parent 
CO  CO 


o 

Benzopyrono  Dibenzopyrone 

(coumarin).  (xanthone). 

substances  of  a  large  and  interesting  variety  of  natural  colouring 
matters  belonging  to  the  chrysin  family,  the  structure  of  which  has 
been  determined  in  the  majority  of  cases  by  synthesis.  A  study  of 
these  compounds  is  beyond  the  scope  of  the  present  chapter. 

EEFERENCE. 
Dte  heterocyJclischen  Verbintiungen,  by  E.  Wedekind.    Veit,  Leipzig,  PJ01. 


CHAPTER  IV 
DYNAMICS  OF  OKGANIC  KEACTIONS 

OF  the  various  means  which  have  been  employed  to  obtain  in- 
formation in  regard  to  the  mechanism  of  organic  reactions,  one  of 
the  most  important  is  that  afforded  by  a  study  of  the  velocity  of 
change,  and  of  the  way  in  which  this  velocity  is  modified  by 
variations  in  the  conditions  under  which  a  given  reaction  occurs. 
In  the  early  study  of  chemical  dynamics,  chief  interest  centred  in 
the  discovery  of  simple  reactions,  which,  by  reason  of  their  freedom 
from  any  disturbing  complications,  might  be  made  use  of  in  testing 
the  applicability  of  the  law  of  mass  action  to  account  for  the  observed 
course  of  the  change.  Now,  however,  that  the  mass  law,  under 
given  conditions  with  respect  to  temperature  and  the  nature  of  the 
reaction  medium,  has  been  definitely  established  as  the  factor  which 
determines  the  course  of  a  given  change,  the  main  object  of  a  dynamical 
investigation  lies  in  the  information  which  it  affords  in  regard  to  the 
mechanism  by  which  the  final  products  of  a  reaction  are  produced 
from  the  original  substances. 

LAW  OF  MASS  ACTION 

Historical.  That  chemical  change  is  not  entirely  determined  by 
the  operation  of  specific  chemical  affinities  appears  to  have  first  been 
recognized  by  Wenzel1  (1777),  who,  from  his  observations  on  the  rate 
of  solution  of  metals  in  acids,  arrived  at  the  conclusion  that  the  rate  of 
chemical  action  is  proportional  to  the  concentration  of  the  substances 
entering  into  the  reaction.  A  similar  view  was  put  forward  by  Ber- 
thottetmhisEssaideStati2ueChimique(18()3).  The  fact  that  Berthollet's 
views,  supported  as  they  were  by  experimental  evidence  of  a  convincing 
kind,  had  but  little  influence  on  the  trend  of  chemical  theory  at  this 
period  was  doubtless  due  in  large  measure  to  the  erroneous  conclusion 
which  he  drew  in  regard  to  the  influence  of  mass  on  the  composition 
of  chemical  compounds.  The  proof  that  such  composition  is  quite 
independent  of  the  quantities  of  the  reacting  substances  tended  to 

1  Lehre  von  der  chemischen  Verwandtschajt  der  Korper,  1777. 
12 


276  DYNAMICS  OF  ORGANIC  REACTIONS 

bring  the  whole  doctrine  of  mass  action  into  disrepute,  and  for  many 
years  no  further  progress  was  made  in  the  direction  indicated  by 
Berthollet's  researches. 

In  the  fifties  Rose  *  and  Malaguti 2  called  attention  to  phenomena 
which  undoubtedly  indicated  the  important  part  played  by  the 
quantities  of  the  reacting  substances  in  chemical  change,  but  no 
generalization  of  any  importance  was  drawn  by  these  observers. 
About  the  same  time,  Wilhelmy 3  studied  the  inversion  of  sucrose 
under  the  influence  of  acids,  and  arrived  at  the  conclusion  that  the 
rate  of  transformation  of  the  sucrose  is  at  every  moment  proportional 
to  its  concentration.  The  agreement  of  the  experimental  data  with 
the  values,  calculated  from  the  equation  which  Wilhelmy  deduced  on 
the  basis  of  the  above  proportionality,  represents  the  first  definite 
proof  of  the  operation  of  mass  in  a  chemical  reaction  according  to 
a  quantitative  law  (Part  III,  chap.  96). 

Somewhat  later,  Berthelot  and  St.  Gilles,4  in  a  detailed  study  of 
the  formation  and  decomposition  of  the  esters,  showed  that  the 
relative  masses  of  the  various  substances  involved  determined  the 
direction  of  the  change.  Whether  change  occurs  in  accordance  with 
the  upper  or  lower  arrows  in  the  formula 

C2H6OH  +  CH3 .  C02H  ^±  CH3 .  C02C2H5  +  H20 

depends,  at  a  given  temperature,  on  the  relative  quantities  of  the 
four  substances  concerned. 

The  part  played  by  quantity  or  the  mode  of  operation  of  mass 
in  chemical  change  was  first  enunciated,  however,  in  the  form  of 
a  generalized  statement  by  Guldberg  and  Waage6  in  1867.  If 
A  and  B  represent  two  substances  which  are  decomposed  into  A' 
and  B',  and  it  is  assumed  that  under  the  same  conditions  Af  and  B' 
can  react  to  form  A  and  J9,  then,  under  the  influence  of  the  chemical 
affinities  and  the  active  masses  of  the  reacting  substances,  a  state  of 
equilibrium  will  be  reached  which  can  be  represented  in  the  follow- 
ing manner.  If  the  active  masses  of  -4,  B,  A'  and  Bf  be  denoted  by 
jp,  q,  p'  and  #'  respectively,  and  the  affinity  coefficients  of  the  reactions 
A  +  B—*A'  +  B'  and  A'  +  B'  — »•  A  +  B  are  represented  by  k  and//, 
then  in  the  condition  of  equilibrium  Jcpq  —  ~k'p'(±  or  k/Jtf  =p'c['/pq.  = 
constant.  From  experiments  in  which  barium  sulphate  was  treated 
with  differently  concentrated  solutions  of  potassium  carbonate,  or 

1  Ann.  Physik,  1855,  94,  481 ;  1855,  95,  96,  284,  426. 

2  Ann.  Chim.  Phys.,  1867  (3),  51,  828. 

8  Ann.  Physikj  1850,  81,  413;  Ostwald's  Klassiker,  No.  29. 

4  Ann.  Chim.  Phys.,  1862  (3),  65,  885  ;  1862  (3),  66,  5;  1863  (3),  68,  225. 

5  Ostwald's  Klassiker,  No.  104. 


HISTORICAL  277 

with  solutions  containing  both  potassium  carbonate  and  sulphate,  it 
was  shown  that  the  equilibrium  condition  in  the  reversible  change 
BaS04  +  K2C03  ^±  BaC03  4  K2S04  is  in  agreement  with  the  require- 
ments of  this  theory.  In  the  equilibrium  state,  the  opposing  reactions 
are  exactly  balanced,  and  the  velocities  of  two  opposed  reactions  are 
accordingly  measured  by  Jcpq  and  Jc'p'q'  respectively.  In  other  words, 
the  rate  of  progress  of  a  change  in  which  several  substances  react 
together  is  determined  by  a  specific  constant  and  by  the  product  of 
the  active  masses  of  the  reacting  substances. 

In  the  further  development  of  this  idea,  a  certain  amount  of  con- 
fusion arose  in  connection  with  the  question  whether  the  mass  effect 
is  solely  dependent  on  the  number  of  the  reacting  substances  or  on  the 
number  of  the  molecules  of  those  substances  which  are  involved  in 
the  actual  molecular  interchange.  Kinetic  considerations  indicate 
that  the  latter  view  is  the  correct  one,  and  thermodynamical  reason- 
ing leads  to  the  same  result. 

Unimolecular  Non-reversible  Reactions.  From  the  molecular 
kinetic  standpoint,  the  simplest  chemical  changes  are  those  in  which 
the  product  or  products  of  a  reaction  are  directly  formed  as  a  result  of 
the  transformation  of  the  individual  molecules  of  the  original  sub- 
stance. Such  changes,  which  are  not  dependent  on  the  interaction 
of  two  or  more  molecules,  are  solely  determined  by  the  law  of 
probability.  It  is  obvious  that  reactions  which  belong  to  this  class 
are  necessarily  limited  to  certain  types.  Amongst  them  we  find 
changes  in  which  complex  molecules  are  decomposed  into  simpler 
molecules  and  those  in  which  intramolecular  rearrangements  are 
involved.  Although  no  reaction  may  be  said  to  be  absolutely  irre- 
versible, those  which  belong  to  this  group  are  characterized  by  the 
absence  of  any  appreciable  tendency  on  the  part  of  the  product  or 
products  of  the  reaction  to  react  with  the  formation  of  the  original 
substance. 

From  the  fact  that  a  uniinolecular  change  is  not  dependent  on  the 
interaction  of  two  or  more  molecules,  and  therefore  of  the  approach 
of  such  molecules  within  the  range  of  intermolecular  influence,  it  is 
evident  that  the  speed  of  a  unimolecular  change  is  entirely  in- 
dependent of  the  spacial  distribution  of  the  molecules,  that  is  to  say, 
of  the  volume  occupied  by  a  given  quantity  of  the  substance.  Close 
packing  of  the  molecules,  which,  in  all  cases  where  intermolecular 
actions  are  concerned,  is  conducive  to  increased  speed  of  reaction, 
has  no  influence  on  the  velocity  of  a  unimolecular  change. 

If  a  represents  the  original  quantity  of  a  substance  per  unit  of 


278  DYNAMICS  OF  ORGANIC  REACTIONS 

volume,  (a  -  x)  the  quantity  present  after  time  t,  then  at  this  moment 
the  velocity  of  the  unimolecular  change  is  given  by 

dx/dt  =  Jcl(a-x)    (1) 
which  yields  on  integration 


Throughout  the  course  of  the  reaction,  the  expression  on  the  right 
side  of  the  equation  (2)  must  remain  constant,  and  \  ,  which  is  the 
so-called  velocity  coefficient,  is  solely  determined  by  the  specific 
character  of  the  reaction,  provided  that  the  temperature  and  the 
nature  of  the  medium,  in  which  the  change  occurs,  are  prescribed. 

From  equation  (1)  it  is  evident  that  the  velocity  coefficient  re- 
presents the  quantity  of  the  original  substance  which  would  be 
transformed  in  unit  time,  if  throughout  this  period  of  time  the  con- 
centration were  maintained  constant  and  equal  to  unity. 

If  the  integrated  form  of  the  equation  is  considered,  it  is  further 
obvious  that  the  time  required  for  the  transformation  of  a  given 
fraction  (l/n)  of  the  original  substance  is  independent  of  the  initial 
concentration,  for  a/(a  -x)  —  n/(n  -  1),  and  equation  (1)  may  there- 
fore be  written  in  the  form 


~  If  v    M     1 
"i     n-  L 

It  is  also  clear  that  the  value  of  the  velocity  coefficient  of  the  uni- 
molecular change  is  not  in  any  way  influenced  by  the  particular  unit 
in  terms  of  which  the  concentration  is  expressed. 

Velocity  of  Intramolecular  Rearrangement  in  Halogen 
Acetanilides.  This  intramolecular  change  affords  an  example  of 
a  unimolecular  non-reversible  reaction.  In  presence  of  hydrogen 
chloride,  acetylchloroanilide,  for  example,  is  gradually  transformed 
into  4?-chloroacetanilide  in  accordance  with  the  formula  (Part  II, 
p.  371)i 

CH  CC1 

HC/\CH  HC/ScH 


HC\/CHXC1 

O.N<  C.N< 

XX).CH3  XX).  CH. 

The  rate  of  progress  of  the  change  can  be  readily  followed  by 
removing  samples  and  adding  them  to  excess  of  a  potassium  iodide 

1  J.  J.  Blanksma,  Eec.  Trav.  Chim.  des  Pays-Bas,  1902,  21,  366 ;  1903,  22,  290. 


UNIMOLECULAK  NON-REVERSIBLE  REACTIONS    279 

solution  and  titration  of  the  liberated  iodine.  This  iodine  corresponds 
with  the  undecomposed  acetylchloroanilide  present,  for  the  ^-chloro- 
acetanilide  is  without  action  on  the  iodide.  The  following  data  were 
obtained  in  20  %  acetic  acid  solution  at  25°. 

t  (hours)  a—x  (in  c.c.  of  standard  Jc 
Na2SaO8  solution) 

0  49-3  — 

1  35.6  0-139 

2  25-75  0-140 

3  18-5  0-140 

4  13-8  0-138 
6  7.3  0.138 
8  4-8  0-139 

As  the  numbers  in  the  third  column  indicate,  the  progress  of  the 
reaction  can  be  satisfactorily  accounted  for  on  the  assumption  that 
the  reaction  is  unimolecular,  or  of  the  first  order.1 

Polyinolecular  Non-reversible  Reactions.  In  contrast  with 
changes  of  the  first  order,  the  speed  of  a  reaction,  which  involves  the 
interaction  of  two  or  more  molecules,  increases  as  the  volume  con- 
taining a  given  quantity  of  the  original  substance  or  substances 
decreases.  Such  diminution  in  volume  is  accompanied  by  an  increase 
in  the  frequency  with  which  the  molecules  enter  into  collision  or 
come  within  the  range  at  which  interaction  between  the  several 
molecules  becomes  possible.  This  concentration  effect,  which  be- 
comes more  pronounced  as  the  order  of  the  reaction  increases,  finds 
adequate  expression  in  the  equation  which  is  obtained  when  the  law 
of  mass  action  is  applied  to  a  reaction  of  the  second  or  higher  order. 

In  the  many  reactions  which  belong  to  this  group,  the  molecules 
actually  involved  in  the  change  may  be  all  identical,  or  in  part  so,  or 
they  may  all  be  different.  So  far  as  the  dynamical  course  of  the 
reaction  is  concerned,  the  nature  of  the  reacting  molecules  is,  how- 
ever, of  no  importance,  the  progress  of  the  change  during  successive 
time  intervals  being  solely  determined  by  the  number  of  the  mole- 
cules involved  in  the  actual  process  of  molecular  interchange. 

Bimolecular  Reactions.  Changes  belonging  to  the  polymolecular 
non-reversible  group  are  of  the  most  varied  nature,  and  include  poly- 
merisation phenomena,  synthetic  reactions,  double  decompositions, 
isomeric  changes,  &c.  As  a  first  example,  we  may  consider  the 
saponification  of  esters  by  the  alkali  hydroxides.  In  the 'case  of 

1  In  view  of  the  observations  of  Orton  it  would  appear  that  the  intramolecular 
change  of  the  chloroamine  involves  two  stages  and  is  therefore  a  composite  re- 
action ;  cf.  Orton  and  King,  Trans.  Chem.  Soc.,  1911,  99,  1869;  also  Orton  and 
Jones,  Trans.  Chem.  Soc.,  1909,  95,  1456. 


280  DYNAMICS  OF  ORGANIC  REACTIONS 

a  simple  ester  (that  is,  the  ester  of  a  monobasic  acid)  the  reaction 
is  bimolecular,  two  molecules  being  involved,  as  indicated  by  the 
ordinary  chemical  equation 

CH3  .  C02C2H5  +  NaOH  =  CH3  .  C02Na  +  C2H3OH 

The  saponification  proceeds  at  a  rate  which  can  be  conveniently 
measured  at  temperatures  between  0°  and  25°  if  dilute  solutions  are 
employed.  If  the  original  solution  contains  a  grm.-mols.  (mols)  of 
ester  and  b  mols  of  hydroxide  per  unit  volume,  and  if  x  mols  of  ester 
have  been  saponified  after  time  t,  the  concentrations  of  the  reacting 
substances  at  this  moment  will  be  a-x  and  b-x  respectively. 
According  to  the  mass  law,  the  speed  of  the  change  will  be  given  by 

dx/dt  =  k2(a-x)(b-x) 
and  this  on  integration  becomes 

7.  1  7       *(»-*). 

/12~~  (a-b)t       a  (b-x) 

In  the  following  table  are  given  the  data  obtained  by  Reicher  l  for 
the  saponification  of  ethyl  acetate  at  15-8°,  the  alkali  being  present 
in  excess  (b  >  a)  in  the  one  experiment,  whilst  the  ester  predominated 
in  the  second  (a  >  b).  The  quantities  of  saponified  ester  (x)  are  ex- 
pressed in  terms  of  the  standard  acid  solution  which  was  used  in 
following  the  progress  of  the  change. 

Excess  of  alkali  hydroxide.  Excess  of  ester. 

t  (minutes)  x  fca                  t  (minutes)            x  £2 

0  o  —  0                   o  — 

3-74  7-76  3-47  2-57  8-23  345 

6.29  11.49  348  5-03  13-09  3-46 

10.48  15-81  3.43  7-35  17.97  3-45 

13-60  18-22  3-44  9-57  20.93  3-41 

oo  29-03  —  oo  21-12  — 

If  the  reacting  substances  are  present  in  equivalent  proportions 
(a  =  b),  the  rate  of  change  at  time  t  is  given  by 

dx/dt  =  Jc.2(a-  x)2 
from  which 


t  a(a-x) 

That  this  is  in  agreement  with  the  actual  course  of  saponification 
under  these  conditions  is  shown  by  the  following  data  for  an  experi- 
ment at  24-7°  with  a  solution  in  which  the  concentrations  of  both  ester 
and  alkali  hydroxide  were  0-025  mol  per  litre.2 

1  Annalen,  1885,  228,  257  ;  1886,  232,  103  ;  1887,  238,  276. 

2  Arrhenius,  Zdt.phys.  Cham.,  1887,  1,  110. 


BIMOLECULAR  REACTIONS  281 

t  (minutes}  a—x  (in  c.c.  of  standard                 f:3 

acid} 

0  8-04 

4  5-30  0-0159 

6  4-58  0-0157 

8  3-91  0-0164 

10  3-51  0-0160 

12  3-12  0-0163 

15  2-74                    •        00160 

20  2-22  0-0163 

Saponification  experiments  with  different  bases  have  shown  that 
the  reaction  only  proceeds  in  accordance  with  the  above  equations  in 
the  case  of  the  strong  bases,  that  is  to  say,  those  which  are  almost 
completely  ionised  in  dilute  solution.  With  weak  bases  the  rate  of 
saponification  falls  off  very  much  more  quickly  than  would  be  antici- 
pated on  the  assumption  that  the  velocity  is  at  every  moment  pro- 
portional to  the  product  of  the  concentrations  of  the  ester  and  the 
base.  If,  however,  we  assume  that  the  active  mass  of  the  base  is 
represented  by  that  portion  which  is  ionised,  in  other  words,  that 
saponification  is  due  to  the  hydroxyl  ion,  the  differences  in  the 
behaviour  of  strong  and  weak  bases  can  be  accounted  for  quite 
readily.  From  these  observations  it  is  necessary  to  conclude  that 
the  saponification  of  an  ester  should  be  represented  by  the  equation 

CH3 .  CO2C2H5  +  OH'  =  CH3 .  CO/  +  C2H5OH 

Termolecular  Non-reversible  Reactions.  According  to  Noyes 
and  Cottle,1  the  reduction  of  silver  acetate  by  sodium  formate  in 
dilute  aqueous  solution  affords  an  instance  of  an  organic  reaction  in 
which  three  molecules  are  involved  in  the  intermolecular  transaction 
which  gives  rise  to  the  products  of  the  change.  The  order  of  the 
reaction  is  therefore  in  agreement  with  what  would  be  anticipated  on 
the  basis  of  the  ordinary  chemical  equation, 

HC02Na  +  2CH3 .  CO,Ag  =  2Ag  +  CH5C02Ka  +  CH.C02H  +  C02 
or,  HCO2'  +  2Ag*  =  H'  +  CO2  +  2Ag 

In  the  investigation  of  the  progress  of  this  reduction  process,  ex- 
periments were  made  at  100°,  samples  of  the  reaction  mixture  being 
forced  over  from  the  steam-jacketed  tube  into  an  ice-cold  solution  of 
potassium  thiocyanate.  By  this  means  the  reaction  was  brought  to 
a  standstill  and  the  unchanged  silver  salt  reacted  with  an  equivalent 
quantity  of  the  thiocyanate. 

Denoting  the  initial  equivalent  concentrations  of  the  formate  and 
acetate  by  a  and  ?>,  then,  if  the  reaction  is  of  the  third  order,  the  rate  of 

1  Zeit.  physik.  Chem.,  1898,  27,  579. 


282  DYNAMICS  OF  OKGANIC  KEACTIONS 

change  when  the  original  concentration  has  diminished  by  x  will  be 
given  by 


and  this  can  be  integrated  and  the  termolecular  velocity  coefficient 
Jc3  evaluated  in  terms  of  a,  6,  x,  and  t. 

The  following  data  were  obtained  in  an  experiment  in  which  the 
initial  a  and  &  values  were  each  equal  to  0-05.  For  comparative  pur- 
poses the  values  of  the  bimolecular  velocity  coefficient  7c2  are  also 
given  in  the  fourth  column  : 

t  (minutes)  x  k3  k2 

00  _  — 

3  0-00967  35-8  1-60 

8  0-01841  37-6  146 

16  0-02532  38-8  L28 

25  0-02952  37-6  1-16 

45  0-03371  37-4  0.92 

80  0-03950  37-5  0-75 

Comparison  of  the  numbers  under  Jc3  and  k.2  shows  that  the  former 
series  is  practically  constant,  whereas  those  of  the  latter  series  fall 
continuously  as  the  reaction  proceeds.  In  other  experiments  with 
different  initial  concentrations,  the  new  values  obtained  for  the 
termolecular  velocity  coefficient  are  approximately  the  same  as  in 
the  example  given  above,  and  from  this  the  authors  conclude  that 
the  reaction  in  question  is  really  termolecular. 

The  number  of  such  termolecular  reactions  is  very  limited,  but 
a  further  example  has  been  found  by  van  't  Hoff  in  the  polymerisation 
of  cyanic  acid,  the  mechanism  of  which  is  therefore  in  accordance 
with  the  equation  ordinarily  employed  to  represent  the  polymerisa- 
tion process,  namely, 

3HCNO  =  (HCNO)3 

In  general,  reactions  of  a  higher  order  are  quite  exceptional.  In  the 
bromination  of  benzene,  in  presence  of  iodine  as  catalyst,  Bruner 
claims  to  have  found  an  example  of  a  quadrimolecular  reaction,  and, 
if  his  conclusion  is  accepted,  this  reaction  probably  represents,  from 
the  point  of  view  of  the  intermolecular  transaction  which  is  involved, 
the  most  complicated  instance  of  a  non-reversible  organic  change 
which  has  been  dynamically  investigated  up  to  the  present. 

Determination  of  the  Order  of  a  Reaction.  Since  the  ex- 
pressions for  the  velocity  coefficients  of  reactions  of  the  first,  second, 
third,  &c.,  order  are  quite  different  in  form,  it  is  evident  that  dyna- 
mical data  may  be  utilised  in  drawing  conclusions  relating  to  the 
mechanism  of  any  given  change.  In  the  following  discussion  of  the 
methods  which  may  be  employed  in  such  investigations,  it  will  be 


ORDER  OF  A  REACTION  283 

assumed  that  the  reactions  in  question  are  of  the  non-reversible  type 
and  that  the  final  products  are  directly  formed  from  the  initial 
reacting  substances. 

Velocity  Coefficient  Method.  The  most  obvious  method  of  pro- 
cedure consists  in  the  utilization  of  the  dynamical  data  to  calculate 
the  uni-,  bi-,  ter-,  and  quadri-molecular  velocity  coefficients.  Accord- 
ing to  whether  Jc1,  fc2,  fr3,  or  &4  remains  constant,  the  conclusion 
might  be  drawn  that  the  reaction  is  of  the  first,  second,  third,  or 
fourth  order.  Although  the  application  of  this  method  has  led  to 
results  which,  in  a  large  number  of  cases,  leave  no  room  for  doubt 
as  to  their  validity,  experience  has  shown  that  erroneous  deductions 
may  not  infrequently  be  made  from  the  observed  constancy  of  one  or 
other  of  the  expressions  for  the  velocity  coefficients.  If,  as  the 
reaction  proceeds,  disturbances  arise  in  consequence  of  the  action  of 
one  of  the  final  products  on  one  or  other  of  the  original  substances, 
it  is  evident  that  the  data  representing  the  progress  of  the  reaction 
may  indicate  the  constancy  of  a  velocity  coefficient  which  does  not 
correspond  with  the  re#l  order  of  the  reaction.  On  this  account, 
measurements  relating  to  the  initial  stages  of  the  reaction  will  in 
general  furnish  a  more  satisfactory  basis  for  the  deduction  of  the 
order  of  the  change. 

Initial  Velocity  Method.  This  method,  first  employed  by 
van  't  Hoif,1  involves  the  determination  of  the  speed  in  the  early 
stages  of  the  reaction  and  of  its  dependence  on  the  concentration  of 
the  original  substance  or  substances.  If  the  reacting  substances  are 
present  in  equivalent  proportions,  the  average  speed  ^  during  the 
initial  stage  of  the  reaction  will  be  given  by 


where  Ox  is  the  average  concentration  of  the  reacting  substances 
during  the  time  interval  A^  and  n  is  the  order  of  the  reaction.     If  ' 
C2  is  the  average  concentration  during  a  similar  time  interval  A£2  in 
a  second  experiment,  then 


From  (1)  and  (2)  c  n 


or  logy,-  log  tfr 

log  4-  log  C, 

1  Studies  in  Clienrical  Dynamics,  by  J.  H.  van  't  Hoff,  trans,  by  T.  Ewan.  Williams 
&  Norgate  (18%). 


284  DYNAMICS  OF  ORGANIC  REACTIONS 

In  carrying  out  experiments  to  determine  n  in  this  way,  the  con- 
centrations Ci  and  C2  should  not  be  too  nearly  equal,  and  the  time 
intervals  should  be  chosen  so  as  to  allow  of  the  accurate  estimation 
of  the  average  speed  during  this  period.  The  magnitude  of  the 
initial  period  will  be  determined  by  the  accuracy  with  which  the 
progress  of  the  reaction  can  be  followed,  but  as  a  general  rule  it  will 
be  convenient  to  choose  the  time  intervals  in  such  a  way  that 
from  10-20  per  cent,  of  the  reacting  substances  have  disappeared.  In 
practice,  this  method  is  particularly  useful  in  cases  where  the  final 
products  give  rise  to  disturbing  secondary  reactions,  for  such  products 
will  obviously  have  least  influence  when  the  quantities  formed  are 
relatively  small. 

Method  of  Equifractional  Farts.  This  method,  which  was 
first  suggested  by  Ostwald,1  consists  in  comparing  the  times  which 
are  required  for  the  decomposition  of  the  same  fractional  amount  of 
the  reacting  substances,  when  the  initial  concentration  is  varied.  If 
we  compare  the  influence  of  the  concentration  on  the  time  required 
for  the  disappearance  of  a  definite  fraction  (1/w)  of  the  original  reaction 
mixture,  by  reference  to  the  expressions  for  the  velocity  coefficients 
of  reactions  of  the  first,  second,  and  third  order  with  equivalent  con- 
centrations of  the  reacting  substances,  it  is  seen  that  this  influence 
is  quite  different  in  the  several  cases : 

Unimolecular  reaction,    t  =  T  In -r  ,  that  is,  t  is  independent 

KI      a-  a/n 

of  a. 

Bimolecular  reaction,      t  =  -  .     ,  that  is,  t  varies  inversely 

Jc2a(a-  a/n) ' 

as  a. 

Termolecular  reaction,  t  =  -  ^L^"  /  \z  »  that  is>  i  varies  in' 
versely  as  a2. 

From  the  above  relationships  it  is  evident  that  experiments,  in 
which  the  concentration  of  the  reaction  mixture  is  varied,  afford 
a  simple  means  of  determining  the  mechanism  of  the  irreversible 
change.  Disturbances  from  side  reactions  (see  later)  are  to  a  large 
extent  eliminated  by  this  method  of  procedure,  and  only  influence 
the  result  obtained,  in  so  far  as  the  relative  importance  of  the  side- 
reactions  varies  with  the  concentration  of  the  reacting  substances. 
By  comparison  of  the  time  intervals  required  for  the  disappearance 
of  successive  equifractional  amounts  of  the  original  substances  in 
parallel  experiments  with  different  initial  concentrations,  an  estimate 
1  Zeit.physik.  Cliem.,  1888,  2,  127. 


ISOLATION  METHOD  285 

may  be  formed  of  the  extent  to  which  the  principal  reaction   is 
disturbed  by  subsidiary  reactions  in  its  different  stages. 

Isolation  Method.  As  its  name  implies,  this  method  consists  in 
arranging  the  conditions  of  the  dynamic  experiments  so  that  one  of 
the  reacting  substances  is  isolated  from  the  rest  in  so  far  as  its 
influence  on  the  course  of  the  reaction  is  concerned.  This  can  be 
effected  quite  readily,  for  the  condition  of  isolation  is  attained  if  the 
concentrations  of  the  reacting  substances  are  so  arranged  that  the 
active  masses  of  all  but  one  remain  sensibly  constant  during  the 
whole  process. 

If  A  and  B  react  in  accordance  with  the  equation 

mA  +  nB  —  »jpC7+  ql>+  ... 

and  B  is  present  in  relatively  large  amount,  then  according  to  the 
law  of  mass  action 

A  _  i,nm    rn  . 

~df    -ICA'C*' 

but  since  CD  is  practically  constant,  the  rate  of  change  may  be  written 


and  according  to  this  equation  the  course  of  the  reaction  will  be 
determined  by  the  number  (m)  of  molecules  of  the  isolated  substance 
A  which  are  involved  in  the  actual  process  of  molecular  interchange, 
although  m  +  n  molecules  are  in  reality  involved.  In  a  similar  manner, 
the  value  of  n  may  be  determined  in  a  separate  series  of  experiments 
in  which  the  substance  B  is  isolated.  In  the  case  of  more  complicated 
reactions,  this  method  is  of  great  utility,  and  has  been  frequently 
applied  in  the  systematic  investigation  of  organic  reactions. 

By  application  of  one  or  more  of  the  above  methods,  it  is  possible 
to  obtain  information  in  regard  to  the  part  played  by  each  of  the 
several  substances  which  take  part  in  a  chemical  change.  Although 
in  the  discussion  of  these  methods  it  has  been  presumed  that  the 
reactions  are  simple  and  irreversible,  the  application  is  by  no  means 
limited  to  reactions  of  this  type.  Under  suitable  conditions  the 
methods  may  also  be  applied  to  the  more  complex  changes  in  which 
simultaneous  or  consecutive  reactions  are  involved. 

In  the  following  pages  examples  will  be  given  of  reactions  which 
have  been  investigated  in  this  manner. 

Stereo-chemical  Changes.  In  view  of  the  simple  character  of 
the  isomeric  transformation,  the  dynamical  course  of  stereo-chemical 


286  DYNAMICS  OF  ORGANIC  REACTIONS 

changes  is  of  particular  interest.  The  investigation  of  the  rate  of 
conversion  of  syn-aldoxime  acetates  into  the  corresponding  anti- 
forms  by  Ley,1  has  shown  that  the  reaction  proceeds  in  accordance 
with  the  unimolecular  equation. 

The  change  occurs  in  absolute  alcoholic  solution  in  presence  of 
hydrogen  chloride  as  catalyst,  and  can  be  followed  by  the  addition 
of  removed  samples  of  the  solution  to  an  ice-cold  aqueous  solution  of 
sodium  acetate,  the  mixture  being  then  heated  for  some  time  at  80°, 
when  the  unchanged  syn-aldoxime  acetate  is  converted  into  the  corre- 
sponding nitrite  with  the  liberation  of  acetic  acid,  which  is  titrated 
with  standard  alkali.  The  following  data  were  obtained  in  an 
experiment  with  anis-syn-aldoxime  acetate  at  25°  in  presence  of  0-01 
normal  HC1  as  catalyst. 

t  (minutes)  a—x  kj.  =  —  log  — 

0  0-0100  — 

10  0.00554  0-0256 

20  0-00318  0-0248 

30  0.00199  0-0239 

40  0-00118  0-0255 

In  regard  to  the  catalytic  action  of  the  acid,  it  may  be  supposed 
that  an  intermediate  additive  compound  is  formed,  and  that  this 
undergoes  stereo-isomeric  change,  the  acid  being  subsequently 
liberated  from  the  isomeric  form  as  represented  by  the  formula 

K.C.H  E.C.H  R.C.H 


N.COaCH3  C1.N.C02CH3  CHo.C09.N.Cl 

I  I 

H  H 

K.C.H 

->  ||         +  HC1 

CH3.C02.N 

In  this  connection,  reference  may  be  made  to  the  remarks  on 
catalytic  reactions  on  p.  826. 

Conversion  of  Diazoamino-  into  Aminoazo-compounds.  The 
transformation  of  diazoaminobenzene  into  aminoazobenzene,  which 
takes  place  when  aniline  hydrochloride  or  other  aniline  salt  is  added 
to  an  aniline  solution  of  the  diazoamino-compound,  affords  a  further 
instance  of  an  intramolecular  change  which  has  been  investigated 
dynamically.  The  speed  can  be  measured  conveniently  at  25°-50°, 
samples  of  the  reaction  mixture  being  run  into  caustic  soda  solution 
in  order  to  stop  the  reaction,  and  the  unchanged  diazoamino-compound 
1  Zeit.  physik.  Chem.,  1895,  18,  376. 


CONVERSION  OF  DIAZOAMINO-COMPOUNDS         287 

estimated  by  boiling  with  dilute  acid  and  collecting  the  nitrogen 
which  is  liberated  by  its  decomposition. 

The  experimental  data  obtained  by  Goldschmidt  and  Reinders1 
show  that  the  reaction  progresses  in  accordance  with  the  equation 
for  a  unimolecular  change.  For  a  given  concentration  of  the  diazo- 
amino-compound,  the  velocity  coefficient  is  proportional  to  the 
concentration  of  the  aniline  hydrochloride.  On  the  other  hand, 
when  the  concentration  of  the  aniline  salt  is  fixed,  experiments 
with  different  concentrations  of  the  diazoamino-compound  lead  to 
practically  the  same  value  of  the  velocity  coefficient. 

These  observations  indicate  that  the  aniline  hydrochloride  plays  the 
part  of  a  catalyst  in  the  transformation  of  the  diazoamino-compound. 

When  other  aniline  salts,  e.  g.  the  trichloracetate  and  dichlor- 
acetate,  are  substituted  for  the  hydrochloride,  the  nature  of  the 
reaction  is  unchanged,  but  the  velocity  coefficients  show  appreciable 
differences. 

For  solutions  containing  0-5  mol  diazoaminobenzene  and  0-1  mol 
aniline  salt  per  litre,  the  velocity  coefficients  at  25°  were  found  to 
be  0-0060,  0-00437,  and  0-00205  for  the  chloride,  trichloracetate, 
and  dichloracetate  respectively.2  Since  the  speed  of  the  reaction 
diminishes  with  the  strength  of  the  acid,  it  is  supposed  that  the 
catalytically  active  components  are  not  really  the  aniline  salts,  but 
the  free  acids  which  result  from  their  dissociation. 

Apropos  of  this  reaction,  reference  may  be  made  to  the  fact  that 
aminoazobenzene  is  formed  when  diazoaminobenzenetoluene  is 
dissolved  in  aniline  in  presence  of  an  aniline  salt.  Dynamic 
measurements  show  that  the  speed  of  this  reaction  is  identical  with 
that  observed  in  the  transformation  of  diazoaminobenzene,  and  it 
therefore  seems  probable  that  the  diazoaminobenzenetoluene  is 
primarily  transformed  into  diazoaminobenzene  in  accordance  with 
the  equation 
C6H5N  :  N  .  NHCGH4  .  CH3  +  C6H5NH2  =  C0H5 .  N :  N .  NHC6H5 

+  CH3.C6H4.NH2 

Hydrolysis  of  Sucrose  and  Esters.  As  already  mentioned,  the 
study  of  the  inversion  of  aqueous  solutions  of  sucrose  in  presence  of 
acids  afforded  the  first  proof  that  reaction  velocity  is  at  every 
moment  proportional  to  the  concentration  of  the  decomposing 
substance.  In  accordance  with  the  equation 

C12H22On  +  H20->C6H1206  +  C6H1206, 

the  reaction  is  bimolecular  and  its  rate  of  progress  is  found  to  be  in 
1  Ber.,  1896,  29,  1369.  2  Bert)  1396,  29,  1899. 


288  DYNAMICS  OF  ORGANIC  REACTIONS 

agreement  with  the  dynamic  equation  for  a  bimolecular  change.  Since 
in  sucrose  solutions,  which  are  not  too  concentrated,  the  water  is 
present  in  considerable  excess,  its  active  mass  remains  practically 
constant,  and  it  is  therefore  not  surprising  to  find  that  the  values 
obtained  for  the  unimolecular  velocity  coefficient  7^  exhibit  much 
the  same  degree  of  constancy  as  the  values  of  the  bimolecular  co- 
efficient A*2  (Part  III,  p.  96). 

If  a  and   b  are  the   concentrations   of  the  sucrose  and   water 

respectively,  then  A;.,  =  , TT-,  In  ,-7 -;,  and  since  x  is  at  all  times 

(a  -  b)  t      b(a-x) 

very  small  in  comparison  with  b,  the  equation  may  obviously  be 
written  in  the  same  form  as  the  equation  for  a  true  unimolecular 

change,  viz.  i          a 

Jc.  =  --  In 

t       a-x 

The  speed  of  the  sucrose  inversion  may  be  readily  followed  by 
observations  of  the  rotation  of  a  beam  of  plane  polarised  light,  and 
if  «0,  <ty  and  -  otx  denote  the  rotations  at  the  commencement,  after 
time  t  and  when  the  rotation  has  reached  its  final  value,  it  is  obvious 
that  a0  -f  ax  affords  a  measure  of  a,  and  a,  +  aM  a  similar  measure  of  a  -  x. 

The  following  table  contains  the  data  for  the  inversion  of  a 
20  per  cent,  solution  of  sucrose  at  25°  under  the  influence  of  0-5 
normal  lactic  acid.  For  this  solution  the  values  of  a  and  b  may  be 
taken  as  0-628  and  45-3  respectively.  The  observed  rotations  after 
measured  time  intervals  are  shown  in  the  second  column  ;  the 
numbers  in  the  third  and  fourth  give  the  values  of  a-x  and  b-x, 
and  columns  5  and  6  show  that  the  uni-  and  bi-molecular  velocity 
coefficients  remain  satisfactorily  constant.  The  inversion  of  cane 
sugar  by  an  acid  in  aqueous  solution  affords  therefore  an  instance 
of  a  bimolecular  change,  the  course  of  which  is  represented  quite 
satisfactorily  by  the  equation  for  a  unimolecular  reaction.1 


t  (minutes) 

a 

a—x 

l-x 

fci.  10* 

A-2.  10* 

0 

-i-  34-50° 

0-628 

45-3 

— 

— 

1435 

31-10° 

0-581 

45.3 

0-235 

0.525 

4315 

25.00° 

0496 

45-2 

0-236 

0-526 

7070 

20.16° 

0-429 

45-1 

0-234 

0-517 

11360 

13-98° 

0-343 

45-0 

0-231 

0-511 

14170 

10-61° 

0-297 

45-0 

0-230 

0-509 

16940 

7-57° 

0-254 

44-9 

0-232 

0-514 

19820 

5.08° 

0-220 

44.9 

0-229 

0-510 

29930  -1.65°  0.126  44-8  0-233  0-518 

oo  -10-77°  0  44.7  —  — 

1  Although  the  inversion  of  sucrose  and  similar  changes  are  often  quoted  as 
examples  of  reactions  of  the  first  order,  it  seems  to  the  author  that  this  is 
a  misnomer,  for  the  apparent  unimolecular  character  of  these  changes  is  entirely 
determined  by  the  particular  concentration  relationships  obtaining  under  the 
usual  conditions  in  which  the  reactions  are  carried  out. 


HYDROLYSIS  OF  SUCROSE  AND  ESTERS  289 

The  polarimetric  method  employed  in  following  the  progress  of 
sucrose  hydrolysis  affords  an  example  of  the  application  of  physical 
methods  in  determining  the  quantities  of  substances  in  solution. 
Although  such  methods  may  in  certain  cases  afford  accurate  results, 
it  seems  likely  that  the  accuracy  attainable  in  the  polarimetric  method 
of  determining  the  speed  of  the  inversion  of  sucrose  has  been  exag- 
gerated. Not  only  has  the  hydrolysing  acid  an  influence  on  the 
rotatory  powers  of  the  different  sugars  involved  in  the  chemical 
change,  but  the  fact  that  glucose  and  laevulose  undergo  muta- 
rotation  will  also  have  an  influence  on  the  observed  rotation. 
Under  these  circumstances  it  seems  improbable  that  the  polarimetric 
data  afford  a  measure  of  the  rate  of  change,  which  is  as  reliable  as 
that  attainable  in  the  case  where  chemical  methods  of  estimation 
are  employed. 

It  has  been  supposed  that  the  hydrolysis  of  sucrose  by  dilute 
acids  deviates  from  the  requirements  of  the  mass  law  as  expressed 
by  the  uni-  or  bi-molecular  equation  and  that  in  the  early  stages  of 
the  reaction  the  velocity  is  practically  constant.1  This  linear  period 
is  undoubtedly  characteristic  of  the  hydrolytic  change  when  brought 
about  by  small  quantities  of  enzymes.  Recent  experiments 2  indicate, 
however,  that  the  analogy  between  acid  and  enzyme  hydrolysis, 
which  would  be  indicated  by  such  a  parallelism,  has  no  foundation 
in  fact,  and  that,  within  the  limits  of  experimental  error,  the  rate  of 
sucrose  hydrolysis,  both  under  the  influence  of  very  dilute  and  more 
concentrated  acids,  is  at  all  stages  determined  by  the  concentration 
of  non-hydrolysed  substances. 

The  process  of  ester  hydrolysis  in  dilute  aqueous  solution  under 
the  catalytic  influence  of  acids  is  in  many  respects  similar  to  sugar 
inversion  from  the  dynamic  point  of  view.  Although  it  has  been 
shown  recently  *  that  the  hydrolysis  of  methyl  acetate  in  presence  of 
hydrochloric  acid  does  not  proceed  to  completion,  but  that  an  equili- 
brium condition  is  reached  when  about  95  per  cent,  of  the  ester  has 
been  hydrolysed,  yet  for  practical  purposes  the  reaction  may  be 
regarded  as  non-re versible.  The  data  representing  the  progress  of 
the  change  are  found  to  give  a  satisfactorily  constant  value  for  the 
unimolecular  velocity  coefficient,  a  circumstance  which  is  due  to  the 
relatively  large  active  mass  of  the  water,  for,  in  reality,  the  process 
of  ester  hydrolysis  is  a  bimolecular  change. 

1  Armstrong  and  Caldwell,  Proc.  Roy.  Soc.,  1904,  A,  74,  195. 

2  Worley,  Proc.  Roy.  Soc.,  1912,  A,  87,  555;  cf.  also  Rosanoff,  Clark,  and  Sibley, 
Journ.  Amer.  Chem.  Soc.,  1911,  33,  1911. 

3  Worley,  Proc.  Roy.  Sue.,  1912,  A  87,  582. 

PT    I  U 


290  DYNAMICS  OF  ORGANIC  REACTIONS 

Both  the  above  reactions  have  been  largely  used  as  a  means  of 
measuring  the  relative  affinities  of  acids,  for  in  dilute  acid  solutions 
the  speed  of  both  is  very  nearly  proportional  to  the  hydrogen  ion 
concentration.  The  relative  affinity  values,  obtained  in  this  way,  are 
parallel  with  the  affinity  coefficients  obtained  by  electrical  conduc- 
tivity measurements,  and,  on  this  account,  the  two  reactions  have 
played  an  important  part  in  connection  with  the  development  of  the 
hydrogen  ion  theory  of  acids. 

Esterification  in  Alcoholic  Solution.  In  many  respects  this 
reaction  resembles  the  two  which  have  just  been  discussed,  for 
according  to  the  equation 

CH3 .  C02H  +  C2H5OH  -»  CH3 .  C02C2H5  *  H2O, 

we  have  to  deal  with  a  bimolecular  change,  which,  in  consequence  of 
the  large  excess  of  alcohol,  may  be  expected  to  take  place  in  accordance 
with  the  unimolecular  formula.  In  presence  of  an  acid  catalyst  this 
is  actually  the  case,  as  may  be  seen  from  the  data  in  the  following 
table  for  the  esterifi cation  of  acetic  acid  in  presence  of  hydrochloric 
acid.1  In  the  parallel  experiment  are  given  the  data  obtained  in 
the  esterification  of  phenyl  acetic  acid  in  presence  of  picric  acid  as 
catalyst.2 

Acetic  acid  0-1  mol,  HC1 0-025  mol  per  litre.  Phenylacetic  acid  0-2372  mol  per  litre. 

Temperature  14-5°.  Temperature  25°. 

t  (hours)         a  -  x  (in  c,c.  alkali)         fcj  t  (hours)  a  —  x  (in  c.c.  alkali)  kt 

0  604  0  11-86  — 

1  55.1  0.0399  2-3  10-73  0-0187 

2  50.3  0-0397  16-3  6-37  0-0166 

3  45.9  0-0397  21-9  5-39  0.0156 

4  41-9  0.0397  42.1  2-70  0-0152 

5  38-2  0-0398  65-0  1-31  0-0147 

6  34-9  0-0397 

Although  the  numbers  under  ^  are  quite  constant  in  the  acetic 
acid  experiment,  there  is  a  marked  diminution  in  the  successive  values 
of  &J  in  the  case  of  the  phenylacetic  acid.  The  difference  is  no 
doubt  connected  with  the  fact  that  small  quantities  of  water,  when 
added  to  water-free  alcohol,  reduce  the  velocity  of  esterification  to 
a  very  large  extent.3  Since  water  is  formed  by  the  esterification 
of  the  acid,  it  may  be  expected  that  this  will  have  a  retarding 
influence  on  the  progress  of  the  change  if  the  alcohol  employed  as 
solvent  is  nearly  anhydrous.  If,  on  the  other  hand,  water  is  present 
in  the  alcohol  in  larger  proportion,  that  which  is  formed  during  the 

1  Sudborongh  and  Lloyd,  Trans.  Chem.  Soc.,  1899,  75,  467. 

2  Goldschmidt  and  Wachs,  Ber.,  1896,  29,  2208. 

8  Goldschmidl.  Ber.,  1895,  28,  3218  ;  1896,  29,  220S.  Goldschmidt  and  Sunde, 
Ber.t  1906,  39,  7li.  Goldschmidt  and  Udby,  Zeit.  physik.  Chem.,  1907,  60,  728. 


ESTERIFICATION  IN  ALCOHOLIC  SOLUTION       291 

reaction  will  have  comparatively  little  influence  on  the  progress  of 
the  reaction.  It  seems  probable,  therefore,  that  the  difference  between 
the  two  results  is  due  to  the  difference  in  water  content  of  the  alcohol 
used  in  the  esterification,  a  satisfactory  constant  being  obtained  only 
when  the  alcohol  is  not  too  '  dry '. 

The  retarding  influence  of  water  on  the  esterification  process  is  by 
no  means  characteristic  of  this  reaction,  for  the  velocities  of  many 
other  acid-catalysed  reactions  are  also  depressed  to  a  very  large 
extent  on  the  addition  of  very  small  quantities  of  water.1  It  is 
probable  that  the  phenomenon  is  due  to  a  change  in  the  catalyst, 
the  acid  being  very  much  more  active  in  alcoholic  solution  than  it 
is  in  aqueous  solution.  Since  dilute  aqueous  and  alcoholic  solutions 
of  the  mineral  acids  are  both  ionised  to  about  the  same  extent, 
according  to  conductivity  measurements,  it  follows  that  the  ordinary 
acid  ions  which  are  responsible  for  the  transport  of  the  electric 
current  through  the  solutions  cannot  be  regarded  as  the  agents 
responsible  for  the  catalytic  activity.  Various  considerations  indi- 
cate that  the  electrolytic  hydrogen  ions,  present  in  aqueous  solutions 
of  acids,  are  hydrated,-  and  it  is  therefore  possible  that  the  catalyti- 
cally  active  ions  are  the  simple  unhydrated  hydrogen  ions.  In  the 
aqueous  solution  of  a  mineral  acid,  the  proportion  of  such  simple 
ions  must  be  much  smaller  than  in  a  corresponding  alcoholic  solution, 
the  difference  in  concentration  being  determined  by  the  difference  in 
the  affinity  of  the  simple  hydrogen  ions  for  water  on  the  one  hand, 
as  compared  with  their  affinity  for  alcohol  on  the  other.2 

In  the  absence  of  a  catalysing  acid,  the  esterification  of  an  acid  in 
alcoholic  solution  proceeds  otherwise.  Whereas  the  experimental 
data  yield  decreasing  values  for  the  unimolecular  velocity  coefficient, 
fairly  constant  numbers  are  obtained  when  the  bimolecular  coefficient 
is  calculated.  According  to  Goldschmidt,  this  is  a  consequence  of 
auto-catalysis,5  the  speed  of  the  reaction  being  determined  by  the 
concentration  of  the  acid  and  also  by  that  of  the  hydrogen  ions  to 
which  it  gives  rise  by  its  electrolytic  dissociation.  If,  at  a  given 
moment,  the  concentration  of  the"  non-esterified  acid  is  a  -  x,  and  m 
is  the  degree  of  ionisation,  then  m  (a  —  x)  is  the  hydrogen  ion  concen- 

1  Cf.  Lapworth  and  Fitzgerald,  Trans.  Chem.  Soc.,  1908,  93,  2163;  Lapworth, 
ibid.,  2187;  Lapworth  and  Partington,  ibid.,  1910,97,  19;  Dawson,  Trans.  Chem. 
Soc.,  1911,  99,  1 ;  Bredigand  Fraenkel,  Ber.,  1906,  39,  1756  ;  Tubandt  and  Mohr, 
Annalen,  1907,  354,  259. 

2  Cf.  Lapworth,  loc.  tit.  ;  Dawson,  loc.  cit. 

5  Ber.,  1896,  29,  2208.  In  a  later  paper,  ZeiLf.  Elektrochemic,  1909,  15,  4,  Gold- 
schmidt adopts  the  view  that  this  reaction  is  of  a  secondary  character,  the 
primary  reaction  being  due  to  the  presence  of  very  reactive  double  or  complex 
molecules. 

u  2 


292  DYNAMICS  OF  ORGANIC  REACTIONS 


tration,  and  dx/dt  =  k/)i(a  —  x)'2.  Assuming  that  m  does  not  vary 
appreciably  over  the  range  of  concentration  involved,  it  is  evident 
that  the  bimolecular  velocity  coefficient  should  remain  constant 
during  the  reaction.  The  following  data  were  obtained  in  an  experi- 
ment with  trichloracetic  acid  (0-2412  mol  per  litre)  at  25°. 

t  (hours}  a  —  x  -- 

t  a  (a—x) 

0  12-06  — 

47.8  11.18  0.00676 

118-0  10-24  0-00626 

191.0  9-24  0-00663 

291-0  8-30  0.00648 

407-5  7-50  0-00618 

672-0  6.07  0-00605 

Although  the  numbers  in  the  third  column  show  that  the  bi- 
molecular coefficient  is  practically  constant,  this  constancy  does  not 
necessarily  mean  that  the  esterification,  in  absence  of  a  catalyst,  is 
auto-catalytic  in  nature,  for  it  can  be  shown  1  that  the  same  form 
of  expression  is  obtained  for  the  velocity  coefficient,  if  it  is  assumed 
that  the  reaction  takes  place  between  the  alcohol  and  the  undissociated 
acid,  or  between  the  alcohol  and  the  ions  of  the  acid.  In  other  words, 
the  bimolecular  nature  of  the  process  is  a  necessary  consequence  of 
the  electrolytic  dissociation  of  the  acid. 

Influence  of  the  Nature  and  Constitution  of  the  Acid  on  the 
Velocity  of  Esterification.  From  the  work  of  numerous  observers 
it  has  been  possible  to  draw  certain  general  conclusions  relative  to 
the  influence  of  the  nature  and  constitution  of  the  acid  on  the  velocity 
with  which  it  is  esterified  in  presence  of  a  mineral  acid  catalyst. 
In  the  fatty  series,2  all  substituted  acetic  acids  are  esterified  more 
slowly  than  acetic  acid  itself,  and  in  the  series  represented  by 
(1)  CH2X  .  CO.H  ;  (2)  CHX2  .  C02H  ;  (3)  CX3  .  C02H  it  appears  that 
the  first  is  always  more  rapidly  esterified  than  the  second  and  the 
second  more  rapidly  than  the  third.  The  velocity  is  independent 
of  the  strength  of  the  acid,  as  measured  by  its  ionisation  constant 
in  aqueous  solution,  and  mainly  depends  on  the  number  and  *  size  ' 
of  the  atoms  or  groups  which  are  substituted  for  hydrogen  in 
the  acetic  acid.  In  the  series  of  mono-substituted  acetic  acids,  the 
methyl  group  has  the  smallest  influence,  the  effect  of  other  sub- 
stituents  increasing  in  the  order  —  chlorine,  phenyl,  bromine,  iodine 
(p.  340). 

In  the  case  of  aromatic  acids,  similar  retarding  influences  are 
apparent,  and  the  effect  of  substitution  in  the  ortho  position  is  very 

1  Donnan,  Ber.,  1896,  29,  2422. 

2  Sudborough  and  Lloyd,  Trans.  Chem.  Soc.,  1899,  75,  467  ;  1898,  73,  81. 


DECOMPOSITION  OF  DIAZO-COMPOUNDS 


293 


much  greater  than  in  the  meta  or  para  position.  From  experiments 
with  the  diortho  substituted  benzoic  acids,  it  appears  that  certain  of 
these  are  esterified  with  extreme  slowness.  That  there  is  no  real 
difference,  however,  between  such  diortho  substituted  acids  and 
other  substituted  benzoic  acids,  such  as  the  steric  hindrance  hypo- 
thesis would  seem  to  suggest,  is  clearly  shown  by  the  fact  that  such 
diortho  substituted  acids  can  be  esterified  completely  and  without 
difficulty  under  favourable  conditions  (p.  340).  * 

In  the  absence  of  a  mineral  acid  catalyst,  the  influence  of  sub- 
stituting groups  on  the  rate  of  esterification  appears  to  be  less 
sharply  defined,  and  no  very  general  relationships  are  exhibited  by 
the  dynamical  data  for  auto-esterification. 

Decomposition  of  Diazo-compounds.  The  decomposition  of 
aqueous  solutions  of  the  diazo-compounds  of  the  benzene  and 
naphthalene  series  affords  a  further  instance  of  a  bimolecular 
reaction  which  proceeds  in  accordance  with  the  equation  for  a  uni- 
molecular  change.2  In  accordance  with  the  equation 

C6H5N :  NCI  +  H20  =  C6H5OH  +  HC1  +  N2 

nitrogen  is  set  free,  and  the  progress  of  the  reaction  can  be  followed 
by  collecting  this  nitrogen  and  determining  the  volume  after 
measured  time  intervals. 

The  velocities  with  which  different  diazo-compounds  are  decom- 
posed vary  enormously,  as  is  evident  from  the  following  data,  which 
express  the  relative  velocities  of  decomposition,  and  afford  therefore 
a  measure  of  the  relative  stabilities  of  aqueous  solutions  of  the  diazo- 
compounds.  In  consequence  of  the  great  differences  in  the  speed  of 
decomposition,  the  diazo-compounds  cannot  all  be  compared  at  one 
and  the  same  temperature,  but,  on  the  assumption  that  the  tempera- 
ture coefficients  of  the  reaction  velocities  are  sensibly  the  same,  it  is 
possible  to  refer  the  actual  data  to  a  common  basis  and  so  obtain 
a  series  of  comparable  numbers. 

Relative  Rates  of  Decomposition  of  Diazobensene  Compounds. 
Diazo-o-nitrobenzene  chloride  1 


-w-nitrobenzene 
-p-nitrobenzene 
-p-sulphnnilic  acid 
-p-toluene  chloride 
-benzene          ,, 
-o-toluene        „ 
-n-toluene 


5-8 
13.7 
132 
250 
2200 
6000 
6500 


1  Rosanoff  and  Prager,  Journ.  Amer.  Chan.  Soc.,  1908,  30,  1895. 

2  Cain  and  Nicoll,  Trans.  Chem.  Soc.,  1902,  81,  1412;  1903,  83,  206.    Hantzsch, 
Per.,  1900,  33,  2517 ;  cf.  also  Hausser  and  Muller.  Bull.  Soc.  C/mn.,  1892  (111),  7. 
7L>1;  1893(111),  0,  353. 


294  DYNAMICS  OF  ORGANIC  REACTIONS 

Formation  of  Azo  Colouring  Matters.    According  to  the  equation 


*H  >0  +  CCH,N  iCH3)2  .  HC1 

X/ 


/N:N.CCH4.N(CH), 
=  C0H4<(  "  -f  HC1 

\S03H 

it  might  be  expected  that  the  reaction  between  ^-diazobenzene- 
sulphonic  acid  and  dimethylaniline  hydrochloride  would  proceed  at 
a  rate  determined  by  the  product  of  the  concentrations  of  the 
sulphonic  acid  and  the  aniline  salt.  When  the  experimental  data  are 
employed  to  calculate  the  bimolecular  velocity  coefficient,  it  is  found, 
however,  that  the  values  vary  considerably  during  the  course  of  the 
reaction.  Moreover,  addition  of  hydrochloric  acid  to  the  solution 
lowers  the  speed  to  a  considerable  extent,  and  it  is  therefore  im- 
probable that  the  undissociated  aniline  salt  or  its  ion  represents  one 
of  the  reacting  components,  for  the  active  mass  of  these  will  not  be 
appreciably  altered  by  the  addition  of  the  acid. 

If,  on  the  other  hand,  it  is  assumed  that  the  free  base  present 
in  the  solution  is  the  active  component,  and  if  the  concentration  of 
this  at  any  moment  be  denoted  by  £  and  the  concentration  of  the 
sulphonic  acid  by  a  -  x,  then 

dx/dt  =  7c£(a  -  x).  (1) 

If,  further,  the  original  reaction  mixture  contains  a  mols  of  dimethyl- 
aniline  hydrochloride  and  &  mols  of  added  hydrochloric  acid  per  litre, 
then  after  time  t,  when  x  mols  of  the  azo-compound  have  been  formed, 
the  concentrations  of  the  hydrochloride,  free  base,and  hydrochloric  acid 
will  be  respectively  (a-g-x),  £,  and  (h  +  g  +  x)  and  from  a  considera- 
tion of  the  hydrolytic  equilibrium 

CCH,  N(CEL)2 .  HC1  +  H2O  ^±  C6H6 .  N(CH,)2II .  OH  -f  HC1 
it  follows  that  (£)(&  +  *  +  *) 

(a-t-x) 

Since  £  can  in  general  be  neglected  in  comparison  with  &  -r  x  and 
a  -  x,  we  may  write 

a-x 

and  by  substituting  in  equation  (1) 

dx/dt  =  Jc 
or 


,       1  ia+l      x  a    } 

k  =  -  \  • _ In \  . 

t  (    a      a-x         a-x) 


FORMATION  OF  AZO  COLOURING  MATTERS        295 

In  the  following  table  are  given  the  data  obtained  by  Goldschmidt 
and  Merz1  in  two  experiments  at  20°  with  different  amounts  of 
added  acid. 

a  =  0-0282,  6  =  0-0232  mot.  a  =  0-0282,  6  =  0-0564  mol 

t  (minutes)  a  —  x         k'  t  (minutes}    a—x  tf 

0  0-0282  0  0-0282  — 

45  0-0228  0-0057  90  0-0224  0-0060 

150  0-0166  0-0057  240  0-0176  0-0056 

210  0-0146  0-0057  375  0-0142 ,  0-0061 

300  0-0118  0-0063  480  0-0123  0-0063 

390  0-0108  0-0058  1440  0-0068  0-0055 

1320  0-0051  0-0056  1800  0-0058  0-0056 

The  retarding  influence  of  the  hydrochloric  acid  is  seen  from  the 
fact  that  whereas  the  reaction  is  approximately  half  completed  in 
210  minutes  in  the  first  experiment,  the  time  required  for  this  in  the 
second  is  about  375  minutes. 

The  constancy  of  Ts,  as  shown  by  the  above  numbers,  together 
with  the  fact  that  neutral  chlorides  are  without  influence  on  the 
speed  of  the  reaction,  indicates  with  considerable  certainty  that 
the  formation  of  methyl  orange  is  due  to  the  interaction  of  the  diazo 
compound  not  with  the  aniline  salt,  but  with  the  small  quantity  of 
free  base  which  is  present  in  the  solution. 

Transformation  of  Ammonium  Cyanate  into  Carbamide.     In 

the  conversion  of  ammonium  cyanate  into  carbamide  in  dilute 
aqueous  solution,  we  have  to  deal  with  a  reaction  which  is  reversible 
to  an  extent  which  is  easily  measurable.  The  composition  of  the 
solution  in  the  final  condition  of  equilibrium  indicates,  however,  that 
the  velocity  of  decomposition  of  the  carbamide  may  be  almost 
neglected  in  comparison  with  the  velocity  of  its  formation,  until  at 
least  75  per  cent,  of  the  cyanate  has  been  transformed,  and,  on  this 
account,  it  is  convenient  to  treat  the  reaction  as  belonging  to  the 
group  of  non-reversible  changes.  A  further  circumstance  which 
complicates  the  process  is  the  simultaneous  decomposition  of  the 
cyanate  with  formation  of  ammonium  carbonate,  but  this  change 
may  also  be  neglected  in  comparison  with  the  principal  reaction. 

The  following  table  contains  data  recorded  by  Walker  and  Hanibly  2 
for  the  decomposition  of  a  0-1  molar  solution  of  cyanate  at  50-1°. 
In  calculating  the  uni-  and  bi-molecular  velocity  coefficients  (kt  and  #2), 
the  concentrations  recorded  under  a  —  x  are  reckoned  from  the  practical 
end-point  of  the  reaction  which  makes  a  =  0-0916  instead  of  0-1. 

1  Eer.,  1897,  30,  670. 

8  Trans.  Chem.  Soc.,  1895,  67,  740. 


296  DYNAMICS  OF  ORGANIC  REACTIONS 

t  (minutes)  a—x  kt  k2 

0  0-0916  — 

45  0-0740  0-00206  0-0576 

72  0-0656  0-00201  0-0599 

107  0-0584  0-00183  0-0577 

157  0-0512  0-00161  0-0548 

230  0-0424  0-00145  0-0551 

312  0-0348  0-00134  0-0572 

600  0-0228  0-00101  0-0548 

Whilst  &!  diminishes  as  the  reaction  proceeds,  the  values  of  l\2  are 
practically  constant,  indicating  that  the  reaction  is  bimolecular. 
To  account  for  this,  it  might  be  supposed  (a)  that  two  molecules 
of  ammonium  cyanate  react  together  ;  (b)  that  the  cyanate  is  dissociated 
into  ammonia  and  cyanic  acid,  which  yield  carbamide  by  their 
interaction  ;  (c)  that  the  reacting  components  are  the  ammonium  and 
cyanate  ions  or  the  non-ionised  ammonium  cyanate.  Whereas  the 
addition  of  neutral  salts  has,  in  general,  no  appreciable  influence  on 
the  velocity  of  the  reaction,  it  is  found  that  ammonium  salts 
increase  the  speed  considerably.  On  the  other  hand,  free  ammonia, 
which  is  but  feebly  ionised  in  solution,  has  little  influence  on  the 
rate  of  change.  From  these  facts  Walker  and  Hambly  drew  the 
conclusion1  that  the  bimolecular  course  of  the  change  is  due  to  the 
interaction  between  the  ammonium  and  cyanate  ions,  carbamide 
being  formed  from  these  as  represented  by 


In  agreement  with  this  view  it  is  found  that  &2  diminishes  some- 
what as  the  initial  concentration  of  the  cyanate  solution  increases, 
this  being  due  to  the  decrease  in  the  ionisation  of  the  salt  as  its 
concentration  increases. 

Most  of  these  facts  can  be  equally  well  interpreted,  however,  if  we 
assume  that  it  is  the  non-ionised  portion  of  the  ammonium  cyanate 
which  undergoes  transformation,  and  the  fact  that  in  90  per  cent. 
ethyl  alcohol,  the  cyanate  is  converted  into  carbamide  thirty  times 
as  rapidly  2  as  in  pure  water  under  similar  conditions,  is  distinctly 
favourable  to  the  view  that  non-ionised  ammonium  cyanate  is  the 
reactive  substance. 

According  to  Chattaway,3  the  transformation  of  the  non-ionized 
cyanate  into  carbamide  is  not  a  case  of  simple  intramolecular 
change,  but  is  due  to  the  interaction  of  ammonia  and  cyanic  acid, 
analogous  to  the  reactions  between  isocyanic  esters  and  ammonia  or 

1  For  a  criticism  of  this  view  compare  E.  E.  Walker,  Proc.  Roy.  Soc.,  1912, 
A  87,  539.  . 

2  Walker  and  Kay,  Trans.  Chem.  Soc.,  1897,  71,  489. 
8  Trans.  Chem.  Soc.,  1912,  101,  170. 


THE  FRIEDEL  CRAFTS  REACTION  297 

amines,   whereby   substituted   carbamides  are  formed.    The  trans- 
formation may  be  formulated  as  follows  : 

XOH 

^±II,N.  CO.  NH3 


and  if  this  view  is  correct,  the  reaction  in  question  belongs  to  the 
group  of  consecutive  reactions  (p.  313). 

The  Friedel-Crafts  Reaction.  Some  light  has  been  thrown  on 
the  mechanism  of  this  general  reaction  by  dynamical  experiments. 
Steele1  has  investigated  in  this  manner  the  formation  of  tolyl 
phenyl  ketone  from  toluene  and  benzoyl  chloride  in  presence  of 
aluminium  chloride  and  of  ferric  chloride  (p.  195).  The  reaction 
corresponds  with  the  equation 

CGH5CO  .  Cl  +  C6H5  .  CH3  =  CCH5.  CO  .  CGH4  .  CH3  +  HC1 
and  its  progress  was  followed  by  passing  a  constant  current  of 
hydrogen,  saturated  with  toluene  vapour  at  the  temperature  of 
the  experiment,  through  the  reaction  mixture  and  measuring  the 
change  in  titre  of  a  standard  solution  of  alkali  through  which  the 
issuing  hydrogen,  .carrying  the  hydrogen  chloride  liberated  by 
the  reaction,  was  passed.  In  these  experiments  the  toluene  was 
present  in  large  excess,  and,  under  these  circumstances,  it  might  be/ 
expected  that  the  reaction  would  be  unimolecular.  The  experimental 
data  show,  however,  that  the  order  of  the  reaction  varies  with^iho 
ratio  of  the  amounts  of  aluminium  chloride  and  benzoyl  chloride, 
being  unimolecular  if  the  ratio  A1C13/CCH5  .  COC1  does  not  exceed 
unity,  and  bimolecular  in  presence  of  excess  of  aluminium  chloride. 

The  results  are  best  explained  by  assuming  the  formation  of 
a  compound  between  one  or  both  of  the  reacting  substances  and  the 
aluminium  chloride,  and  by  the  removal  of  the  latter  from  the  system 
in  combination  with  the  ketone  formed. 

When  the  ratio  A1C1:,.CCH5CO.C1  does  not  exceed  unity,  the 
mechanism  suggested  by  Perrier2  and  Bolseken  3  is  sufficient  to 
explain  the  dynamic  observations.  According  to  this,  a  compound 
is  formed  containing  the  acid  chloride  and  aluminium  chloride  and 
this  reacts  with  the  toluene  according  to  the  formula 

Al,Clfi.  2Ci;H,COCl  +  2C6H,  .  CH;;  ->  A12C1G.2CGH5.CO.C6H4.CH~ 

+  2HC1 
If  this   compound  is  only   soluble   to   a   limited   extent  in    the 

1   Trans.  Chem.  Soc.,  1903,  83,  1470. 

*  Jter.,  1900,  33,  815. 

5  Kec.  trav.  chim.  Pays-Bos,  1900,  19,  19  ;  1901,  20,  102. 


298  DYNAMICS  OF  ORGANIC  REACTIONS 

toluene,  the  rate  of  change  during  the  early  stages  of  the  reaction 
will  be  constant,  because  of  the  constant  active  mass  of  the  compound 
in  the  saturated  solution.  The  actual  data  show  that  the  speed  is 
constant  until  the  aluminium  chloride  ceases  to  exist  as  a  solid 
phase,  and  constant  values  are  only  obtained  for  the  unimolecular 
velocity  coefficient  (&J  if  the  time  measurements  are  reckoned  from 
the  point  at  which  this  occurs. 

That  the  aluminium  chloride  is  removed  from  the  reaction 
mixture  in  combination  with  the  final  product  is  indicated  by  the 
fact  that  one  mol  of  aluminium  chloride  cannot  convert  more  than 
one  mol  of  the  acid  chloride  into  the  ketone.  If  this  were  not  the 
case,  the  regenerated  aluminium  chloride  would  react  with  further 
quantities  of  the  acid  chloride. 

In  order  to  account  for  the  bimolecular  character  of  the  reaction 
in  presence  of  excess  of  aluminium  chloride,  it  is  necessary  to  assume 
that  this  forms  a  similar  additive  compound  with  the  toluene.  The 
actual  reacting  components  are  then  the  two  additive  compounds, 
and  the  rate  at  which  hydrogen  chloride  is  evolved  will  be  governed 
by  the  dynamic  equation  for  a  bimolecular  change  (coefficient  =  Jc2). 

The  following  tables  contain  data  obtained  by  Steele  in  experiments 
under  the  two  different  conditions  referred  to  above. 

A1C13  1-20  gram.  C6H5CO  .  Cl  1-18  gram.  Molar  ratio  =  1-0. 

Toluene  20  c.c.  x  =  HC1  liberated. 

t  (minutes')  x  kL                     x/t    r 

2-75  9-3  —                    3-38 

4-5  15-4  —                    3-43 

7-75  24-9  0-194                  3-23 

13-2?  31-8  0-196 

16-0  33-4  0-200 

21-0  34-6  0-19G 

26-0  35-1  0-195 

oo  35-4 

The  numbers  in  the  fourth  column  under  x/t  show  that  the  speed 
is  constant  in  the  early  stages,  but  the  constancy  of  \  demonstrates 
the  unimolecular  character  of  the  further  progress  of  the  reaction. 

A1C13  2-56  gram.  C6H5CO  .  Cl  1-18  gram.  Molar  ratio  =  2-3. 

Toluene  20  c.c.  x  =  HC1  liberated, 

(minutes')  x  k^ 

2-0  22-5  0-0229 

3-0  2G.4  0-0276 

4-0  28-3  0-0281 

5-0  29-2  0-0266 

6-0  30-1  0-0269 

7-75  31-3  0-0278 

oo  35-4  — 

Composite  Reactions.  In  the  reactions  which  have  so  far  been 
discussed,  it  has  been  assumed  that  a  single  chemical  change 


THE  FKIEDEL-CRAFTS  REACTION  299 

is  involved,  that  this  proceeds  in  a  particular  direction  and 
is  moreover  a  direct  process  in  the  sense  that  the  substances 
obtained  are  the  immediate  products  of  the  interaction  of  the 
original  substances.  The  majority  of  reactions  do  not  satisfy  these 
conditions,  in  that  they  usually  involve  simultaneous  or  con- 
secutive changes,  and,  as  a  group,  these  reactions  may  conveniently 
be  distinguished  from  the  simple  reactions  by  the  term  composite 
reactions. 

To  such  composite  reactions,  an  important  principle  applies  —  the 
principle  of  mutual  independence  of  different  reactions  —  according 
to  which,  when  a  number  of  reactions  occur  simultaneously  in  any 
system,  each  of  the  component  reactions  proceeds  in  conformity 
with  the  mass  law,  and  as  if  it  were  quite  independent  of  the  other 
reactions.  We  have  in  this  principle  a  close  analogy  with  that 
which  determines  the  mechanical  effect  on  a  particle  of  the  simul- 
taneous application  of  a  series  of  different  forces.  According  to  the 
nature  of  the  component  changes,  composite  reactions  may  be 
discussed  under  the  head  of  concurrent,  reversible,  and  consecutive 
reactions. 

Concurrent  Reactions.  If  the  original  substances  A  and  B 
react  together  so  as  to  give  rise  simultaneously  to  two  series  of 
products  in  accordance  with  the  formula 

(  m  A  +  n  B  —  »  pC+  qD 


we  have  to  deal  with  a  case  of  two  simultaneous  concurrent 
reactions. 

The  general  theory  of  such  reactions  has  been  discussed  by 
Wegscheider.1  In  general,  the  ratio  of  the  quantities  of  the  different 
sets  of  products  will  be  dependent  on  the  time  which  has  elapsed 
since  the  commencement  of  the  reaction.  If,  however,  the  number 
of  the  molecules  of  each  of  the  reacting  substances  involved  is  the 
same  for  the  different  concurrent  reactions,  the  ratios  of  the  products 
formed  in  the  several  processes  will  remain  constant  throughout  the 
whole  course  of  the  reaction.  In  the  example  formulated  above,  the 
ratio  of  the  quantities  of  the  two  series  of  products  will  be  constant, 
provided  m  =  w'  and  n  =  n'. 

In  regard  to  the  actual  experimental  investigation  of  reactions 
of  this  class,  we  are  only  concerned  with  those  in  which  the  con- 
current reactions  are  limited  to  two  or  three,  and  where  these  are 

1  Zeit.  physik.  Chem.,  1899,  3O,  593;  cf.  also  Ostwald,  Lehrbuch,  2,  2,  249; 
Mellor,  Chemical  Statics  and  Dynamics,  p.  63. 


300  DYNAMICS  OF  ORGANIC  REACTIONS 

of  simple  type  (unimolecular  or  bimoleeular).  If  \ve  are  dealing  with 
two  reactions,  both  unimolecular  or  both  bimoleeular,  the  quantities 
of  the  two  sets  of  products  will  remain  in  a  constant  ratio,  but  this 
will  not  be  the  case  if  one  reaction  is  unimolecular  and  the  other 
bimoleeular. 

In  the  simplest  case,    where   the  two   concurrent  reactions   are 
of  the  first  order,  as  represented  by 


let  a  be  the  original  quantity  of  A  in  unit  volume,  x  the  quantity 
transformed  after  time  t,  y  and  g  the  quantities  of  B  and  C  formed 
after  this  time  interval,  and  Jcg  and  kc  the  velocity  coefficients  of  the 
two  reactions,  then  we  have 

dx/dt  =  dy/dt  +  de/dt  (1) 

de/dt  ="kc  (a-x)  (3) 

and  therefore  dx/dt  =  (kg  +  kc)  («  -  x)          (4) 

or  on  integration 

kn  +  kc  —  -In—  (5) 

t      ci  —  x 

which  is  identical  with  the  equation  for  a  simple  unimolecular 
reaction. 

In  a  similar  manner,  it  can  be  shown  that  the  integrated  form  of 
the  equation  for  a  pair  of  concurrent  bimoleeular  reactions  is  of  the 
same  type  as  the  corresponding  equation  for  a  simple  bimoleeular 
change. 

From  equations  (2)  and  (3)  we  have 

dy/dt  I  dz/dt  =  y/g  =  kn/kc  =  K   (G) 

or  the  ratio  of  the  quantities  of  the  products  of  the  two  concurrent 
reactions  is  constant  and  equal  to  the  ratio  of  the  velocity  coefficients. 
From  (5)  and  (6)  it  follows  further  that 

K     .1U    a 


K+l     t      a-x 

and' 


a-x 


and  these  equations  furnish  us  with  the  velocity  coefficients  of  the 
separate  concurrent  reactions.  Examples  of  non-  reversible  changes 
of  this  type  will  now  be  considered. 


OXALACETIC  ACID  PHENYLHYDRAZONE          SOI 

Decomposition  of  Oxalacetic  Acid  Fhenylhydrazone.  The 
decomposition  of  pure  aqueous  or  acidified  solutions  of  oxalacetic 
acid  phenylhydrazone,  when  heated  at  100°,  has  been  found  by 
Jones  and  Richardson  l  to  yield  two  different  products  —  (A)  pyruvic 
acid  phenylhydrazone,  (B)  pyrazolonecarboxylic  acid,  as  represented 
by  the  equations 

CO.,H  .  C  .  CH2  .  CO,H  COoH  .  C  .  CH3 

II  ->  ||  +  C02      A. 

N.NHC6H5  N.NHCCH5 

CO2H  .  C  .  CH2  .  CO.H  CCXH  .  C  .  CH2 

->  ||    \CO     +  H20      B. 

N.NHC6H5  N.N.C6H; 

Each  of  the  two  concurrent  reactions  is  unimolecular,  but  the 
second  differs  from  the  first  in  that  it  appears  to  be  catalytically 
accelerated  by  acids.  In  addition  to  the  fact  that  relatively  large 
quantities  of  pyrazolonecarboxylic  acid  are  formed  in  mineral  acid 
solutions  as  compared  with  pure  aqueous  solutions,  reference  may 
be  made  to  the  observation  that  solid  oxalacetic  acid  phenyl- 
hydrazone yields  only  pyrazolonecarboxylic  acid.  Furthermore,  it 
has  been  found  that  a  given  amount  of  the  original  substance  yields 
less  carbon  dioxide  as  the  amount  of  water  in  which  it  is  dissolved 
diminishes,  and  that  in  other  less  strongly  ionising  solvents  (such  as 
pyridine,  toluene),  the  relative  amount  of  carbonic  acid  evolved  is 
greater  than  in  the  case  of  aqueous  solutions.  All  these  facts  agree 
with  the  assumption  that  reaction  B  is  catalytically  accelerated 
by  the  hydrogen  ions  resulting  from  the  electrolytic  dissociation  of 
the  acid  hydrazones.  If  a  is  the  amount  of  the  oxalacetic  hydra- 
zone,  originally  present  in  unit  volume  of  the  solution,  x  the  quantity 
decomposed  after  time  t,  y  and  s  the  quantities  of  pyruvic  acid  phenyl- 
hydrazone (or  carbon  dioxide)  and  pyrazolonecarboxylic  acid  formed, 
!CA  and  fa  the  velocity  coefficients  of  the  reactions  A  and  B,  and  H  the 
concentration  of  the  catalysing  hydrogen  ions,  which  is  supposed  to 
remain  constant  throughout  the  reaction,  then 


tA  +  t,.B-to-x,         (1) 

and  since  x  =  y  +  z     and  y/e  =  constant, 

therefore  x/y  =  constant  and  x/z  =  constant. 

If  now  the  total  amount  of  pyruvic  hydrazone  or  carbon  dioxide 
1  Trans.  Chem.  Sot.,  1902,  81,  1140. 


302  DYNAMICS  OF  ORGANIC  REACTIONS 

formed,  when  the  reaction  is  at  an  end,  is  represented  by  ?/«>, 

then 


and  equation  (1)  may  be  written  in  the  form 

JcA  +  Jc£.H  =  -ln-^-.     (2) 

u  oo    y 

The  progress  of  the  reaction  was  actually  followed  by  measurement 
of  the  volume  of  carbon  dioxide  evolved.  The  following  table  con- 
tains the  data  obtained  in  an  experiment  with  a  solution  containing 
0-1  gram  oxalacetic  acid  phenylhydrazone  in  100  c.c.  of  water.  The 
values  under  y  represent  the  C02  evolved  in  c.c.,  y^  being  equal 
to  320. 


t  (seconds')  y  (kA  +  TsK .  IT] .  10~3 

70                        60  1-06 

130                        80  0-96 

172  100  0-95 

236  125  0-91 

312  150  0-88 

392  175   '  0-88 

480  200  0-89 

720  250  0-92 

From  experiments  with  sulphuric  acid  solutions  containing  from 
rio  *°  -TO  equivalent  of  acid  per  litre  it  was  possible  to  obtain 
the  ratio  of  the  coefficients  fa/fa,  and  from  this  and  the  value  of 
(kA  +  fa  .  H)  the  separate  velocity  coefficients  of  the  concurrent 
reactions  could  be  determined.  At  80°  TCA  was  thus  found  equal 
to  0-000366  and  fa  =  0-0183. 

Chlorination  of  Benzene.  When  benzene  is  chlorinated  in 
presence  of  iodine  monochloride,  substitution  and  addition  occur 
simultaneously  in  accordance  with  the  equations 

j  C6H6  +  C12  =  CCH5C1  +  HC1        A. 

/I    TT    /"^l  T> 

—    l/A.ElftV/l«  **• 


This  composite  reaction  has  been  followed  dynamically  *  by  estima- 
tion of  the  quantity  of  unchanged  chlorine  and  of  the  hydrogen 
chloride  formed,  the  former  affording  a  measure  of  the  sum  of 
the  two  velocities,  the  latter  a  measure  of  the  velocity  of  reaction  A. 
In  pure  benzene  solution  the  course  of  the  change  was  found  to  be  in 
agreement  with  the  equation  for  a  unimolecular  reaction,  but  experi- 
ments with  solutions  containing  variable  quantities  of  benzene 
dissolved  in  carbon  tetrachloride  showed  that  the  speed  of  the 

1  Slator,  Trans.  Chem.  Soc.,  1903,  83,  729. 


CHLORINATION  OF  BENZENE  303 

reaction  is  proportional  to  the  benzene  concentration.  For  given 
concentrations  of  chlorine  and  benzene  the  speed  is  moreover  pro- 
portional to  the  square  of  the  concentration  of  the  catalyst,  so  that 
the  rate  of  disappearance  of  chlorine  may  be  represented  by  the 
equation 


At  every  stage  during  the  reaction,  the  ratio  between  the  amount 
of  chlorine  which  enters  the  benzene  nucleus  and  that  which  forms 
the  hexachloride  remains  constant,  this  ratio  being  equal  to  3-3. 
This  observation  shows  that  the  two  reactions  are  both  unimolecular 
in  presence  of  excess  of  benzene. 

When  stannic  chloride  or  ferric  chloride  is  employed  as  catalyst, 
the  hexachloride  is  not  formed  to  any  appreciable  extent,  whereas 
reaction  B  is  the  only  one  which  occurs  under  the  influence  of  light. 
In  all  cases  the  course  of  the  reaction  is  the  same  as  in  presence  of 
iodine  monochloride,  the  rate  of  disappearance  of  the  chlorine  being 
that  required  by  the  equation  for  a  unimolecular  reaction.  The 
differences  in  the  relative  quantities  of  the  two  products  show,  how- 
ever, that  the  relative  speeds  of  the  concurrent  reactions  may  be 
altered  to  a  very  large  extent  by  suitable  variation  of  the  catalyst. 

Action  of  Silver  Salts  on  Alkyl  Iodides.  When  silver  nit  rat  o 
acts  on  ethyl  iodide  in  absolute  alcoholic  solution,  two  changes  occur 
simultaneously,  as  represented  by  the  equations  l 

(C2H5I  +  AgNO3  +  C2H5OH  =  Agl  +  HN03  +  (C2H5)2O     A. 
(C2H5I  +  AgNO3  =  Agl  +  C2H5NO3  B. 

Experiments  at  25°  show  that  the  proportion  of  silver  nitrate 
which  reacts  according  to  A  amounts  to  70  per  cent.,  and  that 
this  proportion  holds  good  for  the  entire  course  of  the  change. 
From  this  it  may  be  inferred  that  the  reactions  are  concurrent 
and  of  the  same  order. 

The  rate  at  which  the  silver  nitrate  disappears  in  any  given 
experiment  is  in  quite  satisfactory  agreement  with  the  assumption 
that  the  reaction  is  bimolecular,  as  might  be  anticipated  from  the 
chemical  equations.  When,  however,  the  initial  concentration  of 
the  reacting  substances  is  increased,  the  velocity  coefficient  also 
increases,  and  from  this  it  may  be  inferred  that  the  reaction  is 

1  Burke  and  Donnan,  Trans.  Chem.  Soc.,  1904,  85,  555  ;  Zeit.  physik.  Chem.. 
1909,  69,  148. 


304  DYNAMICS  OF  ORGANIC  REACTIONS 

not  really  of  the  second  order.  The  change  in  magnitude  of  the 
velocity  coefficient  is  chiefly  due  to  the  silver  nitrate,  for,  in  ex- 
periments with  constant  silver  nitrate  and  increasing  ethyl  iodide 
concentration,  slightly  falling  values  are  obtained  for  &>.  The 
observed  constancy  of  k.2  throughout  any  one  experiment  is  there- 
fore due,  in  all  probability,  to  the  formation  of  some  substance 
during  the  reaction  which  has  an  accelerating  effect  on  the  velocity 
of  the  change.  Of  the  main  products  of  the  reaction,  ethyl  nitrate 
and  ethyl  ether  are  inactive,  and  nitric  acid  diminishes  the  velocity. 
On  the  other  hand,  the  speed  is  increased  when  nitrates  are  added 
to  the  reaction  mixture,  although  these  substances  produce  no 
alteration  in  the  ratio  of  the  two  sets  of  products  A  and  B.  From 
this  it  might  be  inferred  that  the  undissociated  silver  nitrate  is 
the  particular  component  which  reacts  with  the  alkyl  iodide,  for 
addition  of  nitrates  will  diminish  the  concentration  of  the  silver  ion 
and  increase  that  of  the  undissociated  salt. 

When  silver  lactate  is  substituted  for  the  nitrate,1  the  chemical 
nature  of  the  change  undergoes  no  alteration,  the  ratio  of  the  quanti- 
ties of  the  two  sets  of  products  being  the  same  for  lactate  as  for 
nitrate.  In  the  case  of  the  lactate,  however,  the  accelerating  effect 
referred  to  is  absent,  and  the  values  of  the  bimolecular  velocity 
coefficient  fall  as  the  reaction  proceeds. 

If  it  is  assumed  that  the  reaction  takes  place  between  the  ethyl 
iodide  and  the  undissociated  silver  salt,  the  rate  of  change  at  any 
moment  may  be  written 

dx/dt  =  k(l-*)(a-x)*  (1) 

where  a  is  the  original  concentration  of  both  silver  salt  and  alkyl 
iodide  and  a  the  degree  of  electrolytic  dissociation  of  the  silver  salt. 

Assuming  further  that  the  ionisation  varies  with  the  concentration 
in  accordance  with  the  mass  law, 
then  „ 

JL_(a_*)  =  lf,  (2) 

and  from  (1)  j, 

dx/dt  =  ^(a  -  xY  =  M«  -  *)3    (3) 

Although  a  is  not  very  different  from  unity  at  the  dilutions 
employed  in  the  dynamic  experiments,  it  will  increase  slightly  as  the 

reaction  proceeds,  and  in  consequence  #3  =  -  «2  may  be  expected 
1  Donnaii  and  Potts,  Trans.  Chem,  Soc.,  1910,  97,  1882. 


ACTION  OP  SILVER  SALTS  ON  ALKYL  IODIDES     805 

to  increase  somewhat  during  the  reaction.  The  following  data  show 
that  this  is  actually  the  case  : 

t  (minutes)         0         4-2          11-1          30-1          48-5          84-7          119-0 
a-x  2-89       2-0  1-50          1-00          0-80          0-60  0-50 

A:3  —         0-030        0-028        0-029        0-031        0-033          0-035 

The  velocity  equation  assumes  the  same  form  if  we  suppose  that 
the  iodide  reacts  only  with  the  ions  of  the  silver  salt,  but  the 
increased  speed  of  the  reaction  which  is  observed  on  the  addition 
of  nitrates  to  the  mixture  of  ethyl  iodide  and  silver  nitrate  indicates 
that  the  active  agent  is  represented  by  the  undissociated  silver  salt. 

In  view  of  the  attempts  which  have  been  made  in  recent  years 
to  refer  organic  reactions  to  interactions  of  ions,  this  result  is  of 
special  interest,  for  the  reaction  between  an  ionised  salt  and  an 
organic  halogen  compound  may  be  regarded  as  one  in  which  the 
conditions  are  favourable  to  interionic  action. 

Although  it  might  be  expected  that  the  velocities  of  reaction 
between  silver  nitrate  and  the  iodo-derivatives  of  methane  would 
exhibit  a  regular  gradation,  experiment  shows  that  this  is  not  the 
case.  The  velocity  coefficient  for  iodoform  is  about  one-eighth  of 
that  of  methyl  iodide,  and  the  reactivity  of  methylene  iodide, 
instead  of  having  an  intermediate  value,  is  only  about  one- 
hundredth  of  that  of  iodoform. 

Formation    of    Bisnbstitntion    Products    of    Benzene.     The 

nitration,  sulphonation,  and  halogenation  of  mono- substituted  ben- 
zene derivatives  affords  an  instance  of  a  general  reaction  in  which 
three  concurrent  changes  are  involved,  giving  rise  to  the  forma- 
tion of  ortho-,  meta-,  and  para-disubstitution  products.  Although 
no  satisfactory  explanation  has  been  given  of  the  marked  tendency 
towards  the  production  of  disubstitution  products  belonging  to  one 
or  other  of  these  groups,  it  is  evident  that  the  relative  amounts 
of  the  three  products  in  a  particular  case  are  determined  by  the 
velocities  with  which  the  corresponding  reactions  occur  under 
a  given  set  of  conditions.  By  variation  of  the  conditions  (tempera- 
ture, concentration,  reaction  medium)  the  relative  amounts  undergo 
variation,  and  this  must  be  due  to  differences  in  the  extent  to 
which  the  velocities  of  the  three  reactions  are  affected. 

Although  no  reaction  of  this  kind  has  been  examined 'in  detail, 
the  relative  amounts  of  the  products  formed  under  different  con- 
ditions have  been  investigated  for  the  nitration  of  benzoic  acid  and 
its  methyl  and  ethyl  esters.1  The  proportions  of  the  nitro- 

1  Holleman,  Zeit.  physik.  Chem.,  1899,  31,  79. 
PT.  I  X 


306  DYNAMICS  OF  ORGANIC  REACTIONS 

•substitution  products  must  be  in  the  ratio  of  the  rates  of  forma- 
tion and  therefore  of  the  respective  velocity  coefficients  &0,  &,„,  and 
7cp  for  the  ortho-,  meta-,  and  para-compounds,  the  progress  of  the 
reaction  being  given  by  the  equation 


if  the  nitric  acid  is  present  in  large  excess. 

In  experiments  at  different  temperatures,  Holleman  obtained  the 
following  percentage  proportions  for  the  three  nitro-benzoic  acids  : 

Temperature.  Ortho.  Meta.  Para. 

-30°  14-4  85-0  0-6 

0°  18-5  80-2  1-3 

+  30°  22-3  76-5  1-2 

Reversible  Reactions.  If  the  products  of  a  chemical  change 
react  together  with  the  formation  of  the  original  substances,  and  if 
this  reverse  change  occurs,  under  the  conditions  of  the  direct  reaction, 
with  a  velocity  which  is  of  the  same  order  of  magnitude,  the  reaction 
in  question  belongs  to  the  type  of  opposing,  balanced,  reversible, 
or  counter  reactions.  The  principle  of  the  mutual  independence 
of  different  reactions  applies  to  such  a  case  just  as  to  a  series  of 
concurrent  reactions,  Each  of  the  independent  reactions  has  its 
speed  determined  by  a  certain  velocity  coefficient,  by  the  active 
masses  of  the  molecular  species  concerned,  and  by  the  number  of 
molecules  which  are  involved  in  the  actual  process  of  interaction. 

As  compared  with  a  non-reversible  reaction  of  the  same  order, 
the  apparent  speed  of  such  a  reversible  change  falls  off  more  quickly 
as  the  original  substances  disappear,  because  of  the  fact  that  these 
substances  are  continuously  regenerated  from  the  reaction  products. 
The  velocity  of  the  opposed  reaction  increases  with  the  accumulation 
of  the  products  of  change,  and  since  that  of  the  direct  reaction 
diminishes  during  this  process,  a  point  will  ultimately  be  reached 
where  the  velocities  of  the  two  opposed  reactions  are  equal  to  one 
another.  When  this  condition  has  been  attained  the  system  is  said 
to  be  in  equilibrium,  and,  so  long  as  the  external  conditions  are 
unaltered,  the  quantities  of  the  original  and  final  products  present 
will  remain  absolutely  constant.  If  the  reacting  substances  are 
mixed  at  the  outset  with  the  final  products  in  such  quantities  as 
correspond  with  the  equilibrium  condition,  no  change  will  take 
place.  The  so-called  equilibrium  constant  is  simply  the  ratio  of  the 
velocity  coefficients  of  the  opposing  reactions,  and  as  such  its 
evaluation  affords  but  little  information  in  regard  to  the  mechanism 
of  the  two  opposing  reactions. 


REVERSIBLE  REACTIONS  307 

Amongst  the  many  examples  of  reversible  reactions  which  have 
been  investigated  dynamically,  those  in  which  the  opposing  reactions 
are  both  unimolecular  belong  to  the  simplest  type.  If  such  a  reaction 
is  represented  by  the  formula 


and  if  a  be  the  quantity  of  A  originally  present  in  unit  volume 
(B  being  absent),  x  the  quantity  of  A  decomposed  and  therefore  of  B 
formed  after  time  t,  kt  and  &/  the  velocity  coefficients  of  the  direct 
and  reverse  reactions,  then  the  rate  at  which  A  disappears  is  given 

by  dx/dt  =  \(a  -x)-  \'x.  (I) 

When  the  state  of  equilibrium  is  attained      dx/dt  —  0,      and  if 
the  corresponding  value  of  x  is  £,  then     \(a  -  £)  =  &/  £ 

*'--*-  f 
*?-x~ir3> 

where  K  is  the  equilibrium  constant. 
From  (1)  and  (2)  we  obtain 


and  by  integration 


Since    K  =  /W>     this  equation  may  be  written  so  as  to  give  the 
values  of  the  individual  velocity  coefficients,  and  we  then  obtain 

K    1  Ka  17  Ka_  _ 

tlnKa-K+T~x 


By  substitution  of 
we  obtain  > 


- 

and  V  =  --^^?w-^-,         (5) 
-' 


a  t     £-x  a     t 

and  from  these  i          t 

]:i  +  l;i'  =  --lnJL-.  (C) 

It  should  be  observed  that  equation  (6)  bears  a  close  resemblance 
to  the  equation  for  an  irreversible  unimolecular  change.  The  only 
difference  is  that  the  expression  on  the  right-hand  side  of  (6)  contains 
the  quantity  of  the  original  substance  which  has  disappeared  when 
the  condition  of  equilibrium  is  attained,  in  place  of  the  quantity  of 
this  substance  which  was  initially  present.  If  A;/  is  small  ia 

x  2 


308  DYNAMICS  OF  ORGANIC   REACTIONS 

comparison  with  Jclf  then  £  will  not  be  very  different  from  a  and  the 
equation  for  the  reversible  reaction  passes  over  into  that  for  the 
irreversible  change. 

If  the  opposing  reactions  are  both  of  the  second  order,  or  if  one  of 
them  is  unimolecular  and  the  other  bimolecular,  it  is  possible  by 
a  similar  procedure  to  deduce  equations  in  which  x  and  t  are  ex- 
pressed in  terms  of  the  velocity  coefficients  of  the  two  opposed 
reactions,  but  these  more  complex  cases  will  not  be  considered  here 
from  a  general  standpoint. 

Dynamic  Isomerism  of  Nitro- camphor  and  its  Derivatives.1 
Solutions  of  nitro-camphor  or  other  secondary  nitro-derivatives  of 
camphor  exhibit  the  phenomenon  of  mutarotation.  The  progressive 
change  in  rotatory  power  appears  to  depend  on  a  particular  grouping 
in  the  molecule,  for  the  mutarotation  occurs  in  all  solvents.  It  is 
probable  therefore  that  the  change  involved  is  an  intramolecular 
transformation  which  is  independent  of  any  chemical  interaction 
between  the  nitro-camphor  and  the  solvent  (Part  II,  p.  348). 

In  the  case  of  7r-bromonitro-camphor,  both  isomers  or  isodynamic 
forms  have  been  isolated.  The  normal  form  melts  at  108°,  and  has 
a  rotatory  power  [«]#  =  —  51°  in  3-33  per  cent,  benzene  solution  at 
13°.  The  pseudo  form  melts  at  142°  and  its  rotatory  power 
[QL\D  —  + 188°  in  3-33  per  cent,  benzene  solution  at  15°.  These 
rotation  values  have  reference  to  the  freshly  prepared  solutions  only, 
for  each  solution  changes  gradually  in  its  rotatory  power  and  in  each 
case  the  same  final  rotation  is  obtained  [«]/>  =  +  38°.  This  then  is 
the  rotatory  power  of  an  equilibrium  mixture  of  the  two  isodynamic 
forms,  the  equilibrium  condition  resulting  from  the  equality  of  the 
speeds  of  the  opposed  reactions  represented  by 


CaH,,Br 


/CH.NOo  /C.NOH 

/ 


+_        C8HlsBr 


V/  T*S  -v  •*-" 

normal.  pseudo. 

Measurement  of  the  rotation  of  the  solution  after  suitable  time 
intervals  enables  the  progress  of  the  reaction  to  be  followed  very 
conveniently.  If  r0  denotes  the  initial  rotation  of  a  solution  of  the 
pseudo  form,  r  the  rotation  after  time  t,  and  r^  the  equilibrium 
rotation,  then,  since  x  is  proportional  to  (r0  -  r)  and  £  to  (r0  -  rM ),  we 
may  write  j_  £  1  r  —  r 

1  Lowry,  Trans.  Chem.  See.,  1899,  75,  211 ;  5.  A.  Report,  1904. 


DYNAMIC  ISOMERISM  OF  NITRO-CAMPHOR        309 

In  the  following  table  are  recorded  the  results  obtained  with 
a  5  per  cent,  solution  of  pseudo  7r-bromonitro-cainphor  in  chloroform 
solution  at  140.1 

t  (hours')  r  7  logic  yf^- 

0-2  + 188-3                               — 

3-0  169-0  0-0197 

6-0  156-0  0-0198 

7-0  U6-0  0-0198 

24-0  84-5  0-0197 

72-0  37-3  0-0197 

81-0  35-8  0-0191 

96-0  34-0  0-0184 

oo  31-3 

The  concordance  of  the  numbers  in  the  third  column  affords 
satisfactory  evidence  of  the  correctness  of  the  view  that  the  muta- 
rotation  is  due  to  reversible  isodynamic  change.  Whether  or  no  the 
transformation  of  the  pseudo  or  the  normal  form  is  subjected  to 
dynamic  investigation,  it  is  obvious  that  the  value  of  Jc  +  ft  should 
be  the  same.  In  this  particular  case,  actual  experiment  gave  diver- 
gent values,  for  whereas  l\  +  &/  was  found  to  be  0-0188  from 
observations  of  the  rate  of  transformation  of  a  3-33  per  cent,  benzene 
solution  of  the  pseudo  form,  the  corresponding  value  calculated  from 
the  data  for  the  normal  form  was  only  0-0064.  It  is  very  probable 
that  the  difference  in  the  two  values  is  due  to  secondaiy  disturbances, 
for  the  isodynamic  change  in  question  has  been  shown  to  be 
extremely  sensitive  to  traces  of  impurities. 

In  solvents  which  contain  oxygen  the  velocity  of  the  isomeric 
transformation  is  much  greater  than  in  hydrocarbons,  carbon  di- 
sulphide,  or  chloroform.  Bases  like  piperidine  in  chloroform  and 
benzene  solution,  and  sodium  ethoxide  in  ethyl  alcohol,  accelerate 
the  change  enormously.  Neutral  salts  also  exert  an  accelerating 
effect  although  of  much  smaller  magnitude,  and  the  influence  of  acids 
is  still  less  marked. 

In  general,  the  isodynamic  change  begins  as  soon  as  the  substance 
is  brought  into  solution,  but  anomalous  results  have  been  found  in 
certain  cases.2  In  chloroform  solution,  for  example,  normal  nitro- 
camphor  was  found  to  be  comparatively  stable  ;  this  was  afterwards 
found  to  be  due 3  to  the  presence  of  small  quantities  of  carbonyl 
chloride  (formed  by  oxidation  of  the  chloroform)  which  converts 
any  traces  of  ammonia  or  other  aminic  impurities  into  inert  carb- 
amides  and  so  destroys  their  catalytic  action.  By  the  addition  of 

1  Lowry,  loc.  cit. 

2  Lowry  and  Magson,  Trans.  Chem.  Soc.,  1908,  93,  107. 
8  Lowry  and  Magson,  Trans.  Chem.  Soc.,  1908,  93,  119. 


310  DYNAMICS  OF  ORGANIC  REACTIONS 

small  quantities  of  carbonyl  chloride  (or  other  acid  chlorides),  the 
isodynamic  change  can  also  be  arrested  in  other  solvents. 

From  his  observations  on  the  isodynamic  change  of  the  secondary 
nitro  derivatives  of  camphor,  Lowry  assumes  that  the  presence  of 
a  catalyst  is  necessary  before  the  change  can  occur.  Such  changes, 
which  belong  to  the  keto-enol  type,  are  brought  about  by  substances, 
all  of  which  may  be  represented  by  the  general  formula  HX,  such  as 
water,  alcohols,  acids,  amines,  and  bases,  and  the  way  in  which  these 
act  is  supposed  to  be  by  the  formation  of  addition  compounds,  from 
which  the  catalyst  may  be  eliminated  in  a  different  way  from  that 
in  which  it  entered  into  combination  with  the  original  substance. 

Mutarotatioii  of  the  Mono-saccharoses.1  The  mutarotation 
phenomena  exhibited  by  the  mono-saccharoses  are  closely  similar  to 
those  which  have  been  referred  to  in  the  preceding  section.  The 
a-  and  /?-forms  of  glucose  represent  isodynamic  modifications,  and 
their  aqueous  solutions  exhibit  gradual  changes  in  rotatory  power, 
the  ultimate  rotation  being  the  same  independently  of  whether  the 
original  solution  was  prepared  by  dissolving  the  a-  or  the  /?-form. 
The  equilibrium  mixture  corresponds  with  what  was  at  one  time 
supposed  to  be  a  third  modification  of  glucose  (Part  III,  p.  44).2 

Lactose  shows  exactly  similar  relationships,  and  from  Erdmann's 
observations 8  on  the  rates  of  change  of  the  two  isomeric  forms,  it  has 
been  found 4  that  fa  +  #/)  has  the  same  value  whether  the  sum  of  the 
velocity  coefficients  is  calculated  from  the  direct  or  the  reverse 
reaction.  This  is  shown  by  the  following  data : 

Solution  of  a-lactose.  Solution  of  ft  lactose, 

t  (minutes)        r  frj+fc/                     t  (minutes)  r  ki  +  k^ 

0  84-0°  —  0  39-5° 

60  73-4°  0-00206  60  45-8°           0-00209 

120  67-3°  0-00197  120  49-6°           0-00206 

180  62-9°  0-00203  180  52-2°           0-00212 

240  60-1°  0-00209  240  53-9°           0-00224 

oo  56-0°  oo  56-0° 

Mean  0-00204  Mean  0-00213 

Within  the  limits  of  experimental  error,  the  mean  values  of  \  +  #/ 
are  identical,  and  the  requirements  of  theory  are  therefore  fully 
satisfied  in  this  important  particular. 

1  Cf.  Urech,  Ber.,  1882,  15,  2130;  1883,  16,  2270;  1884,  17,  1547;   1885,  18, 
8047. 

2  Lowry,  Proc.  Chem.  Soc.,  1904,  20,  108;  Tanret,  Bull  Soc.  Chim.,  1871  15.  195, 
349;  1872,17,  802. 

3  Ber.,  1880,  13,  2180. 

4  Hudson,  Zeit.  physik.  Chem.,  1903,  44,  487. 


FORMATION  OF  LACTONES  311 

Formation  of  Lact ones  from  y-  and  8-Hydroxy  Acids.  In  pre- 
sence of  mineral  or  other  strong  acids,  y-hydroxybutyric  acid  is 
partially  converted  into  the  corresponding  lactone,  the  reaction  being 
reversible,  as  represented  by  the  formula 

CH2OH  CH2 

I  /I 

CH2  /    CH2 

^±0  +H20 

CH2  \    CH2 

C02H  CO 

Whereas  the  dehydration  of  the  acid  appears  to  be  a  unimolecular 
process,  the  hydration  of  the  lactone  involves  the  interaction  of  two 
molecules  and  is  therefore  bimolecular.  Since  the  water  is  present 
in  large  excess,  however,  its  active  mass  remains  practically  constant, 
and  on  this  account  the  hydration  may  be  expected  to  proceed  in 
accordance  with  the  equation  for  a  unimolecular  change.  In 
presence  of  a  sufficient  quantity  of  mineral  acid,  which  accelerates 
both  reactions  to  exactly  the  same  extent  since  it  is  without  influence 
on  the  final  equilibrium,  the  reaction  takes  place  at  a  convenient 
speed  at  the  ordinary  temperature  and  can  be  followed  by  titration 
of  the  unchanged  acid  by  means  of  a  standard  solution  of  alkali. 
The  following  data  were  obtained  by  Henry 1  in  an  experiment  at  25° 
with  a  solution  containing  initially  0-1767mol  y-hydroxybutyric  acid 
per  litre,  normal  hydrochloric  acid  being  used  as  catalyst : 

t  (minutes)  x  (in  c.c.  of  alkali  solution)         k^  +  fc/ 
00                                  — 

21  2-41  0-0355 

50  4-96  0-0374 

65  6-10  0-0382 

100  8-11  0-0384 

160  10-35  0-0382 

220  11-55  0-0370 

oo  13-28  =  f 

In  the  absence  of  an  acid  catalyst,  y-hydroxy  acids  are  also  slowly 
converted  into  the  corresponding  lactones  under  the  influence  of  the 
hydrogen  ions  which  are  formed  by  their  own  electrolytic  dissociation. 
Under  these  circumstances,  the  change  affords  an  instance  of  an  auto- 
catalysed  reaction,  and  on  the  assumption  that  the  opposing  reactions 
are  accelerated  in  proportion  to  the  concentration  of  the  hydrogen 
ions  and  that  it  is  the  undissociated  acid  which  undergoes  dehydration, 
it  is  possible  to  obtain  an  expression  for  the  progress  of  the  change 

1  Zeit.  physik.  Chem.,  1892,  10,  96. 


312  DYNAMICS  OF  OKGANIC  KEACTIONS 

which  is  also  in  satisfactoiy  agreement  with  experimental  observa- 
tions (compare  Henry,  loc.  cit.). 

Esterification.  The  formation  of  an  ester  from  the  corresponding 
alcohol  and  acid  affords  an  example  of  a  reversible  bimolecular 
change,  as  might  be  expected  according  to  the  formula 

ROH  +  R'CC^H  ^±  KKXXJUI^O 

When  esterification  or  ester  hydrolysis  occurs  in  aqueous  alcoholic 
solutions  under  the  influence  of  an  acid  catalyst,  the  active  masses 
of  the  alcohol  on  the  one  hand,  and  of  the  water  on  the  other, 
remain  unaltered  during  the  progress  of  the  reaction,  and  in  accor- 
dance with  this  it  has  been  found  that  both  esterification  and  ester 
hydrolysis  proceed  at  a  rate  which  can  be  calculated  from  the  equation 
for  a  reversible  unimolecular  change. 

The  following  data  were  obtained  by  Kistiakowsky 1  for  the  esteri- 
fication of  formic  acid  in  41  per  cent,  alcoholic  solution  at  24-75°. 

Formic  acid,  0-0668  mol  per  litre.  HC1,  0-0262  mol  per  litre. 

t  (minutes)                x  (in  c.c.  of  alkali)  ^                           ki 

00  — 

30                                  1-26  62  106 

70                                  2-72  62  106 

110                                  4-07  63  107 

150                                  5-29  61  105 

240                                  7-10  64  110 

330                                  8-32  63  107 

oo                                  11-48  =  £  — 

When  ethyl  formate  is  hydrolysed  under  the  same  conditions, 
values  of  ^  and  &/  are  obtained  which  are  equal  to  those  recorded  in 
the  above  esterification  experiment. 

From  the  previous  discussion  of  esterification  and  ester  hydrolysis 
(see  pp.  279,  290)  it  appears  that  ester  hydrolysis  in  aqueous  solution 
and  esterification  in  alcoholic  solution  are  changes  which  in  presence 
of  an  acid  catalyst  take  place  in  agreement  with  the  equation  for 
a  non-reversible  unimolecular  reaction,  whilst  in  aqueous  alcoholic 
solutions  both  changes  proceed  in  accordance  with  the  requirements 
of  the  equation  for  a  reversible  unimolecular  reaction.  When  none 
of  the  reacting  substances  is  present  in  large  excess,  the  dynamical 
course  of  both  esterification  and  ester  hydrolysis  can  only  be  repre- 
sented by  the  equation  for  a  reversible  bimolecular  reaction. 

If  equimolecular  quantities  of  ethyl  alcohol  and  acetic  acid  are 
mixed  together  and  the  volume  containing  the  gram  molecular 

1  Zeit  physik.  Chem.   1898,  27,  250. 


ESTERIFICATION  313 

quantity  of  each  is  taken  as  unit  volume,  then  the  rate  of  ester 
formation  will  be  given  at  any  moment  by  the  equation 

dx/dt  =  Jc2  (1  -  x)2  -  V  x2.  (I) 

Since  equilibrium  is  attained  when  almost  exactly  two-thirds  of  the 
reacting  substances  have  been  transformed  into  ester  and  water, 
it  follows  that 

jr  =  fe       _  ^__  =  4.0  /2) 

V      (I-*)2 

By  making  use  of  (2)  in  the  integration  of  (1)  we  obtain  the 
relationship  1       <?_„ 


The  following  table  records  the  observations  of  Berthelot  and 
Saint-Gilles  l  on  the  speed  of  ester  formation  at  the  ordinary  room 
temperature  ;  from  these  data  are  calculated  the  values  of  the 
coefficient  kz  =  4&2'. 

t(days)        0      19  41  64  103         137         167          190         oo 

x  0   0-121       0-200      0-250      0-345      0-421      0-474      0-496      0-677 

fca  =  4fc2'    —  0-0072    0-0061     0-0053     0-0052    0-0056    0-0058    0-0057       — 

From  the  series  of  &2  values,  it  appears  that  the  observed  course 
of  the  reaction  is  in  satisfactory  agreement  with  theory  except  in  the 
initial  stages.  The  apparent  diminution  of  the  speed  during  this 
part  of  the  reaction  is  perhaps  connected  with  the  influence  of  the 
water,  initially  formed,  on  the  properties  of  the  acid,  and,  if  so,  the 
effect  is  analogous  to  that  which  has  been  already  noted  in  the  case 
of  esterification  in  absolute  alcoholic  solution. 

According  to  Knoblauch's  experiments2  the  same  values  are 
obtained  for  the  velocity  coefficients  Jc2  and  fr/  independently  of 
whether  these  are  deduced  from  observations  on  the  speed  of  esteri- 
fication or  of  ester  hydrolysis. 

Conversion  of  Alkyl  Ammonium  Cyanates  into  the  corre- 
sponding Carbaxnides.  Although  the  formation  of  carbamide  from 
ammonium  cyanate  has  been  discussed  on  p.  295  as  a  bimolecular 
non-reversible  change,  this  can  only  be  justified  on  the  ground  that 
the  speed  of  the  reverse  reaction  is  relatively  small.  In  the  case  of 
certain  of  the  alkyl  ammonium  cyanates3  the  difference  in  the 
velocities  of  the  opposed  reactions  is  not  nearly  so  large,  and  it 
becomes  necessary  to  take  the  reverse  transformation  into  account. 

1  Ann.  Chim.  Phys.,  1862  (3),  65,  385  ;  1862  (3),  66,  5  ;  1863  (3),  68,  225. 

2  ZeiL  phvsik.  Chem.,  1897,  22,  268. 

»  Walker  and  Appleyard,  Trans.  Chem.  Soc.,  18%,  60,  193. 


314  DYNAMICS  OF  OKGANIC  RE  ACTIONS 

For  a  dialkyl  ammonium  cyanate  we  have  therefore  a  reversible 
reaction  represented  by 

/NHR 
NH2R,CNO  ^±  C0< 

\NHR 

the  speed  of  formation  of  the  carbamide  at  any  moment  being  given  by 

dx/dt  =  k(a-x)2  -  k'x 

By  integration  of  this  and  the  relation  between  Jo  and  k'  which  is 
afforded  by  the  state  of  equilibrium,  namely  K  =  k'k'  =  ,   _.    ,  k  and 

k'  may  be  evaluated  in  terms  of  a,  £,  xt  and  t,  and  experiment  shows 
that  the  decomposition  of  the  alkyl  ammonium  cyanates  can  be 
adequately  accounted  for  on  the  assumption  that  the  actual  change 
is  the  resultant  of  two  opposed  reactions,  one  of  which  is  bimolecular 
and  the  other  unimolecular. 

In  the  appended  table  are  given  the  values  of  k  and  k'  for  a  series 
of  alkyl  derivatives : 

Cyanate  1007,;  100  A;'  k/k' 

Ammonium  14-4  0-0038  3800 

Methyl  ammonium  13-4  0-0022  6100 

Dimethyl       ,  25-3  0-073  350 


Ethyl 
Diethyl 
/so-amyl 
Ter-amyl 


8-1  0-007  1150 

9-0  0-148  60 

0-2  0-0031  3000 

1-3  0-04  32 


On  comparing  the  values  of  k/k'  for  the  dialkyl  and  the  corre- 
sponding mono-alkyl  derivatives  it  is  seen  that  the  relative  speed  of 
the  reverse  change  is  much  greater  for  the  former  than  for  the  latter. 
In  agreement  with  this  is  the  fact  that  carbamides  are  not  formed  to 
any  appreciable  extent  from  the  tri-alkyl  and  tetra-alkyl  ammonium 
cyanates. 

Consecutive  Reactions.  In  many  reactions  the  number  of  re- 
acting molecules,  which  is  indicated  by  the  dynamical  data,  is  quite 
different  from  that  which  corresponds  with  the  chemical  equation. 
According  to  the  equation  for  the  oxidation  of  oxalic  acid  by  potassium 
permanganate  in  presence  of  sulphuric  acid, 

2KMn04  +  5H2C2O4  +  3H2S04  =  K2S04  +  2MnS04  +  8H20  +  10CO, 

it  might  be  supposed  that  ten  molecules  (2  +  5  +  3)  are  involved  in 
the  intermolecular  transaction  by  which  the  final  products  are 
obtained.  In  general,  however,  the  velocity  curves  of  complicated 
reactions  of  this  character  can  only  be  satisfactorily  interpreted  on 
the  assumption  that  the  actual  change  which  determines  the  velocity 


CONSECUTIVE  REACTIONS  315 

is  of  a  simple  character,  that  is  to  say,  of  the  first,  second,  or  possibly 
the  third  order.  Hence  it  seems  probable  that  such  reactions  take 
place  in  two  or  more  stages  and  belong  to  the  group  of  consecutive 
reactions. 

Such  consecutive  changes  will  exhibit  differences  according  to  the 
number,  the  relative  speeds,  and  the  orders  of  the  successive  stage 
reactions  and  also  according  to  whether  the  component  reactions  are 
reversible  or  irreversible.  Except  in  comparatively  simple  cases, 
the  mathematical  analysis  of  the  dynamics  of  such  composite 
reactions  is  of  a  complicated  character,  and  in  this  chapter  no 
attempt  will  be  made  to  consider  more  than  the  simplest  possible 
case,  namely,  that  of  a  reaction  taking  place  in  two  stages,  each  of 
the  component  reactions  being  irreversible  and  unimolecular.  Such 
a  change  may  be  represented  by  the  formula 

A-*B->C 

(1)      (2) 

If,  initially,  a  mols  of  A  are  present  in  unit  volume,  and  after  time 
t  the  quantities  of  A,  B,  and  C  present  are  x,  y,  and  s  respectively, 
and  if  7i\  and  &2  are  the  velocity  coefficients  of  the  first  and  second 
reactions,  then,  according  to  the  mass  law, 

the  rate  of  disappearance  of  A  is 

dx 
-  -j  =  \x  or  x  =  flC~*i*,  (1) 

ctt 

the  rate  of  formation  of  C  is 

-  -  fc,t/  (») 

dt 

and  the  rate  at  which  B  accumulates  is 
dy  dx      dz 

*-/«-»  -*»•-**    (3) 

Further,  we  have  the  relationship 

x  +  y  +  z  =  a,  (4) 

and  from  equations  (1)  to  (4)  it  can  be  shown  that 

*  -  •-   -       (h  •  c-**  -  *2  •  e-*i'),        (5) 


in  which  the  quantity  z  of  the  final  product,  which  has  been  formed 
after  any  given  time  interval  t,  is  expressed  in  terms  of  the  initial 
concentration  (a)  of  the  original  substance  and  the  velocity  coefficients 
&!  and  &2  of  the  two  consecutive  reactions. 

By  analysis  of  equation  (5)  it  can  be  readily  shown  that  if  the 


316  DYNAMICS  OF  ORGANIC  REACTIONS 

velocity  coefficient  of  one  of  the  component  reactions  is  very  much 
larger  than  that  of  the  other,  the  rate  at  which  C  is  formed  will  be 
determined  by  the  speed  of  the  slow  reaction.  Without  reference  to 
equation  (5),  however,  it  is  quite  obvious  that,  under  these  circum- 
stances, the  speed  of  the  entire  change  will  be  determined  solely  by 
that  of  the  relatively  slow  component,  and  that  the  rapid  component 
reaction  will  be  without  measurable  influence.  Under  these  con- 
ditions it  is  to  be  expected  that  the  progress  of  the  consecutive 
reaction  will  be  the  same  as  that  of  a  simple  reaction  of  the  same 
order.  In  many  cases,  in  fact,  it  may  not  be  possible  to  distinguish 
the  composite  from  the  simple  reaction,  although  a  distinction 
may  be  easily  drawn  in  others.  If  the  first  stage  in  the  change 
A-+B—>C  is  relatively  veiy  slow,  the  rate  at  which  C  is  formed 
will  be  practically  the  same  as  the  rate  at  which  A  disappears,  and 
the  formation  of  the  intermediate  substance  may  be  masked.  On 
the  other  hand,  if  the  first  stage  is  relatively  very  rapid,  the  forma- 
tion of  the  intermediate  substance  becomes  very  obvious,  although 
the  isolation  of  it  from  the  reaction  mixture  may  not  be  feasible. 

If  the  velocity  coefficients  of  the  successive  reactions  are  of  the 
same  order  of  magnitude,  the  relationships  are  much  more  com- 
plicated. So  far  as  the  original  substance  A  is  concerned  the  matter 
is  quite  simple,  for  this  will  disappear  in  accordance  with  the  equation 
for  a  non-reversible  unimolecular  change.  On  the  other  hand,  the 
rate  at  which  C  is  formed  depends  on  the  concentration  of  the  inter- 
mediate substance  B,  and  this  is  obviously  dependent  on  the  speeds 
of  the  two  reactions.  If  the  quantities  of  A,  B,  and  C  present  in  the 
mixture  are  plotted  as  a  function  of  time,  the  curve  for  A  falls 
continuously,  that  representing  C  rises,  but  the  B  curve  first  rises 
and  then  falls,  passing  through  a  maximum.  As  the  quantity  of  B 
increases  from  zero  at  the  commencement  of  the  reaction  to  its 
maximum  value,  the  rate  of  formation  of  the  final  product  increases 
correspondingly,  and  attains  a  maximum  when  B  is  at  its  maximum  ; 
thereafter  the  rate  of  formation  gradually  falls  off.  The  point  at 
which  the  velocity  of  formation  of  the  final  product  reaches  its 
maximum  value  is  clearly  dependent  on  the  relation  between  the 
speeds  of  the  two  successive  reactions. 

Decomposition  of  Carbamide  by  Acids  and  Alkalis.  An  example 
of  a  consecutive  reaction  is  afforded  by  the  hydrolytic  decomposition 
of  carbamide,  investigated  in  detail  by  Fawcett  *  by  experiments  in 
sealed  tubes  at  the  temperature  of  boiling  water. 

1  Zeit.  phijsik.  Chem.,  1902,  41,  601. 


DECOMPOSITION  OP  CARBAMIDE  BY  ACIDS       317 

The  first  stage  consists  in  the  formation  of  ammonium  cyanate, 
which,  in  the  second,  is  converted  into  ammonium  carbonate  in 
accordance  with  the  formulae 

I.     CO(NH2)2  ^±  NH4CNO 
II.     NH4CNO  +  2  H20  ->  (NH4)2C03 

From  determinations  of  the  ammonia  present  after  different  time 
intervals,  it  appears  that  the  final  product  is  formed  at  a  rate  which 
can  be  calculated  from  the  equation  for  a  simple  unimolecular  change. 
This  is  the  case  whether  the  solution  is  acid,  alkaline,  or  neutral,  but 
the  magnitude  of  the  velocity  coefficient  varies  considerably  according 
to  the  nature  of  the  solution,  as  is  shown  by  the  data  in  the  following 
table  : 

Hydrolysis  o/|  normal  carbamide. 

1  ft 

Nature  of  solution  Jc{  =  —    g10  - 

t  Qf  —  00 

TV  normal  HC1  102  x  10~5 

|  normal  NaOH  60  x  10~* 

Neutral  6-8  x  10~6 

In  presence  of  acids,  the  intermediate  substance,  ammonium 
cyanate,  is  decomposed  very  rapidly,  but  more  slowly  in  presence  of 
alkali  hydroxides.  In  neutral  aqueous  solution  the  velocity  cannot  be 
determined,  because  of  the  fact  that  the  cyanate  is  almost  completely 
converted  in  a  very  short  time  into  carbamide  in  accordance  with  the 
equation  for  reaction  I.  Since,  however,  potassium  cyanate  is  decom- 
posed with  considerable  speed  into  potassium  carbonate  and  ammonia 
in  neutral  solution,  it  is  reasonable  to  infer  that  ammonium  cyanate 
will  be  decomposed  with  appreciable  velocity  under  similar  con- 
ditions. 

If  the  original  solution  of  carbamide  contains  a  mols  per  litre,  and 
if  x  mols  have  been  decomposed  after  time  t,  the  speed  of  carbamide 
decomposition  at  this  moment  will  be  given  by 


where  \  and  £/  are  the  coefficients  of  the  opposed  reactions  in  I. 
Since  in  acid  solution  the  cyanate  is  decomposed  at  a  relatively  very 
rapid  rate,  the  actual  concentration  of  the  cyanate  must  be  very  much 
smaller  than  x,  and  in  consequence  the  second  term  on  the  right-hand 
side  of  the  equation  may  be  neglected.  In  dilute  acid  solution  the 
speed  of  the  reaction  will  therefore  be  determined  by  the  velocity 
coefficient  l\  of  the  reaction 

CO(NH2)2  -»  NH4CNO. 


318  DYNAMICS  OF  ORGANIC  REACTIONS 

In  pure  aqueous  solution,  where  the  velocity  of  decomposition 
of  the  cyanate  is  much  smaller  than  in  presence  of  acid,  the  effective 
rate  at  which  carbamide  is  transformed  will  he  diminished  in  conse- 
quence of  the  accumulation  of  ammonium  cyanate  and  its  reconversion 
into  carbamide.  It  is  probable  that  this  operates  to  some  extent  in 
alkaline  solution  (compare  previous  table),  but  a  further  complication 
arises  here  in  that  the  carbamide  appears  to  be  directly  hydrolysed 
by  solutions  of  alkali  hydroxide  without  the  intermediate  formation 
of  ammonium  cyanate.  as  represented  by  the  equation 

CO(NH2)2  +  NaOH  +  H20  =  NaHCO3  +  2  NH3 . 

In  agreement  with  this,  it  is  found  that  the  speed  of  the  reaction 
in  strongly  alkaline  solutions  is  much  greater  than  in  acid  solutions, 
that  is  to  say,  greater  than  corresponds  with  the  velocity  coefficient 
hi*  The  hydrolysis  of  carbamide  by  solutions  of  the  alkali  hydroxides 
is  therefore  a  rather  complex  process,  involving  two  concurrent 
reactions  (direct  and  indirect  hydrolysis),  one  of  which  takes  place  in 
successive  stages. 

Action  of  Halogens  on  Carbonyl  Compounds.  In  reference  to 
the  mechanism  of  the  process  of  substitution  of  hydrogen  in  certain 
compounds  by  halogens,  experimental  evidence  is  available  which 
indicates  that  in  the  case  of  compounds  containing  the  group 
:  CH .  CO,  e.  g.  ketones,  aldehydes,  carboxylic  acids  and  their 
derivatives,  the  substitution  is  not  the  result  of  a  simple  process  but 
of  one  in  which  two  or  more  successive  reactions  are  involved.  As 
a  general  rule,  those  carbonyl  compounds  are  the  most  easily  attached 
which  are  known  to  be  capable  of  conversion  into  their  enolic  forms. 
In  the  comparable  case  of  the  nitro-paraffins  it  has  also  been  observed 
that  these  are  not  capable  of  being  brominated  directly,  but  are  easily 
converted  into  bromo-derivatives  if  first  transformed  into  the  isonitro 
form,  corresponding  with  the  enolic  form  of  carbonyl  compounds. 

In  presence  of  a  mineral  acid,  the  aliphatic  ketones  react  with  the 
halogens  in  dilute  aqueous  solution  at  a  rate  which  can  be  followed 
conveniently  at  the  ordinary  temperature.  When  the  ketone  is 
present  in  large  excess,  the  halogen  disappears  at  a  constant  rate, 
which  is  proportional  to  the  concentration  of  the  ketone  and  the 
acid,  but  is  independent  of  the  concentration  of  the  halogen.1  The 
fact  that  the  velocity  remains  unaltered,  as  the  halogen  disappears 
from  the  reaction  mixture,  indicates  that  the  speed  of  the  halogena- 
tion  process  is  determined  by  a  preliminary  reaction  in  which  the 

1  Lapworth,  Trans.  Chem.  Soc.,  1904,  85,  30  ;  Dawson  and  Leslie,  Trans.  Chem. 
Soc.,  1909,  95,  1860. 


ACTION  OF  HALOGENS  ON  CARBONYL  COMPOUNDS  319 

halogen  is  not  directly  concerned.  It  is  therefore  supposed  that  the 
first  stage  consists  in  the  transformation  of  the  ketone  from  the 
ketonic  to  the  enolic  form,  and  that  this  change  is  catalytically 
accelerated  by  the  acid.  This  slow  isomeric  change  is  then  succeeded 
by  a  relatively  very  rapid  change,  in  which  the  enolic  ketone  reacts 
with  the  halogen  X  in  accordance  with  the  formulae 

I.    CH3.CO.CH3^±CH2:C(OH).CH3 
II.     CH2 :  C(OH) .  CH3  +  X2  -»  CH2X  .  CO .  CH3  +  HX. 

In  support  of  this  view  it  may  be  mentioned  that  the  speed  of  the 
reaction  is  practically  independent  of  the  nature  of  the  halogen. 
This  is  to  be  expected  if  reaction  II  is  a  relatively  very  rapid  change, 
for  the  disappearance  of  the  halogen  will  be  determined  by  the 
velocity  coefficient  of  the  reaction  CH3  .  CO .  CH3  — >  CH2  :  CO .  CH3, 
and,  if  the  active  mass  of  the  acetone  is  practically  constant,  this 
reaction  will  occur  at  constant  speed  which  will  be  quite  independent 
of  the  chemical  nature  of  the  subsequent  rapid  reaction. 

If  the  quantity  of  halogen  per  unit  volume  is  a  mols  at  the  start 
and  x  mols  after  time  t,  then 

-dx/dt  =  k,  (1) 

from  which,  since  x  =  a    when     t  =  0, 

x  =  a-kt.  (2) 

The  following  numbers  were  obtained  in  an  experiment  with 
diethyl  ketone  and  iodine  in  aqueous  alcoholic  solution  containing 
40  volumes  per  cent,  of  alcohol.1  In  the  calculation  of  the  values  of 
x  in  the  third  column,  k  is  made  equal  to  0-000059. 

Diethyl  ketone  0-2532  molper  litre,  H,S04  0-10  molper  litre,  Temp.  25°. 

t  (minutes)  x  (observed)  x  (calculated} 

0  0-00904  (0-00904) 

30  0-00727  0-00727 

60  0-00547  0-00550 

80  0-00430  0-00432 

105  0-00285  0-00284 

120  0-00204  0-00190 

135  0-00129  0-00108 

24  hours  0-00022  — 

The  reaction  evidently  slows  down  a  little  towards  the  end,  but  this 
is  no  doubt  due  to  the  fact  that  the  second  stage  is  also  reversible  in 
character,  although  -  under  the  experimental  conditions  it  may  for 
the  sake  of  simplicity  be  treated  as  irreversible. 

Reaction  between  Halogens  and  Ketones  in  the  absence  of  an 
Acid  Catalyst.  In  the  absence  of  an  acid,  the  interaction  between 

1  Dawson  and  Wheatley,  T.ans.  Chem.  Soc.,  1910,  97,  2048. 


320  DYNAMICS  OF  OKGANIC  REACTIONS 

iodine  and  aqueous  acetone  proceeds  very  slowly  and,  at  the  ordinary 
temperature,  the  loss  of  iodine  during  the  first  two  or  three  days  is 
inappreciable.  As  the  reaction  proceeds,  the  velocity  increases 
continuously  in  consequence  of  the  formation  of  the  gradually 
increasing  quantities  of  hydriodic  acid  which  accelerates  the  primary 
tautomeric  change  in  proportion  to  the  quantity  present.  We  have 
in  this  case  an  example  of  an  auto-accelerated  reaction.  Although 
in  presence  of  mineral  acid  the  rate  of  disappearance  of  the  iodine  is 
only  dependent  on  the  speed  of  formation  of  the  enolic  form  of 
acetone,  the  progress  of  the  auto-accelerated  change  is  determined 
by  the  completion  of  a  series  of  three  consecutive  changes  which  may 
be  represented  thus  : 

I.      CH3  .  CO  .  CH3  ^±  CH2  :  C(OH)  .  CH3 

/I 
II.      CH2:C(OH).CH3  +  I2--»CH2I.C<         .  CH3 

X)H 
/I 
III.     CH2I  .  C<^        .  CH3  ->  CH2I  .  CO  .  CH3  +  HI 

Assuming  that  reactions  II  and  III  are  both  of  high  speed  rela- 
tively to  I,  then  the  concentration  of  the  hydriodic  acid  will,  at  any 
moment,  be  equal  to  the  measured  fall  in  the  iodine  concentration. 
If  the  solution  contains  c  mols  of  acetone  per  litre,  this  being  present 
in  large  excess  compared  with  the  iodine,  and  x  mols  of  iodine  have 
disappeared  after  time  t,  the  speed  of  the  primary  tautomeric  change 
and  therefore  that  of  the  complete  reaction  will  be  given  by 

dx/dt  =  kcx  (1) 

or,  if  xl  and  x2  are  the  values  of  x  after  times  ^  and  £2,  we  obtain 

on  integration  i  x 

7c  =     „*        In  ^      (2) 
c(*a-*i)       *i 

The  following  data  *  show  that  the  actual  progress  of  the  change  is 
in  agreement  with  the  requirements  of  equation  (2).  The  progress 
of  the  reaction  was  observed  by  titration  of  the  residual  iodine. 

c  =  0-272  mol  per  litre.     Original  iodine  concentration  =  0-003976  mol  per  litre. 
Temperature  25°. 

noisier  litre  x 


115  0.003384  0-000592  — 

140  0-002758  0-001218  0-1060 

163  0-001616  0-002360  0-1059 

170  0-001110  0-002866  0-1054 

174  0-000814  0-003162  0-1043 

1  Dawson  and  Fowls,  Trans.  Chem.  Soc.,  1912,  101,  1503. 


OXIDATION  OF  ALCOHOL  321 

Although  these  experiments  show  that  the  third  stage  in  the 
reaction  proceeds  rapidly  in  comparison  with  the  first,  measurements 
of  the  electrical  conductivity  of  the  solution  (the  change  in  which  is 
determined  by  the  hydriodic  acid  set  free)  indicate  that  under  certain 
circumstances  there  is  a  very  appreciable  lag  on  the  part  of  reaction 
III  as  compared  with  II.  When  dilute  iodine  solutions  (0-0002  mol 
per  litre)  are  employed,  it  is  found  that  the  electrical  conductivity  of 
the  solution  increases  for  some  time  after  the  solution  has  become 
colourless,  and  this  is  no  doubt  due  to  the  time  factor  which  is 
involved  in  the  decomposition  of  the  intermediate  iodine  addition 
compound. 

Oxidation  of  Alcohol.  The  oxidation  of  ethyl  alcohol  by  bromine 
in  dilute  aqueous  solution  l  affords  a  further  example  of  a  reaction 
which  takes  place  in  consecutive  stages,  as  represented  by  the  formulae 

I.     C2H5OH  +  Br2  -»  CH3 .  COH  +  2HBr 
II.     CH, .  COH  +  Bi-o  +  H20  -»  CH3  .  CO2H  +  2HBr 

Under  the  same  conditions  reaction  II  takes  place  with  much 
greater  speed  than  I,  but,  in  contrast  with  the  cases  previously 
considered,  the  velocity  of  the  more  rapid  reaction  is  such  that  it  can 
be  measured  quite  readily 3  under  the  same  conditions  as  those  in 
which  the  oxidation  of  alcohol  by  bromine  has  been  investigated. 

When  the  ethyl  alcohol  is  present  in  considerable  excess,  the  speed 
of  the  first  stage  is  solely  dependent  on  the  concentration  of  the  free 
bromine,  and  diminishes  continuously  as  the  oxidation  proceeds.  On 
the  other  hand,  the  speed  of  the  second  reaction  gradually  increases 
as  a  result  of  the  increase  in  the  quantity  of  aldehyde  present. 
When  the  aldehyde  has  accumulated  to  such  an  extent  that  the 
ratio  of  the  alcohol  to  the  aldehyde  concentration  is  equal  to  the 
ratio  of  the  velocity  coefficients  of  the  reactions  II  and  I,  it  is  evident 
that  both  will  then  proceed  at  the  same  rate,  so  that  just  as  much 
aldehyde  is  produced  in  unit  time  from  the  alcohol  as  is  lost  by 
oxidation  to  acetic  acid.  This  equality  in  the  speeds  of  the  two 
reactions  is  obviously  dependent  on  the  circumstance  that  both  are 
of  the  same  '  order '  in  respect  to  the  bromine.  If  this  were  not  the 
case,  the  relative  speeds  would  vary  with  the  amount  of  free  bromine 
present  at  each  stage  of  the  reaction.  The  data  obtained  by 
Bugarszky  are  in  satisfactory  agreement  with  this  view  of  the 
oxidation  process. 

}  Bugarszky,  Zeit.  physik.  Ctom.,  1910,  71,  705. 
*    2  Bugarszky,  Zeit.  physik.  Chem.,  1004,  48,  63. 

PT.  I  Y 


322  DYNAMICS  OF  ORGANIC  REACTIONS 

It  is  of  some  interest  to  note  that  the  action  of  bromine  on  ethyl 
alcohol  dissolved  in  solvents  such  as  carbon  tetrachloride,  carbon 
disulphide,  and  bromobenzene  is  quite  different  from  that  in  water 
solutions,  the  main  product  of  the  reaction  being  ethyl  acetate, 
as  represented  by 

2C2H5OH  +  2Br2  =  CH3 .  C02C2HG  +  4HBr. 

This  is  also  the  change  which  occurs  when  bromine  acts  on  alcohol- 
water  mixtures  containing  80  per  cent,  alcohol.1 

Photo-chemical  Reactions.  Many  organic  reactions  are  known 
which  take  place  only  under  the  influence  of  light.  Such  photo- 
chemical reactions  are  of  two  kinds,  namely  those  in  which  the 
chemical  change  is  reversed  when  the  light  is  cut  off,  and  those  which 
are  non-reversible.  In  the  case  of  certain  reversible  photo-chemical 
changes,  the  final  state  of  equilibrium  has  been  found  to  be  dependent 
on  the  intensity  of  the  light  which  acts  on  the  system,  and  in  such 
cases  it  may  be  inferred  that  the  part  played  by  the  light  rays  is  not 
that  of  an  ordinary  catalyst. 

In  their  experiments  on  the  photo-chemical  combination  of 
hydrogen  and  chlorine,  it  was  shown  by  Bunsen  and  Roscoe 2  that 
the  activity  of  the  rays  from  a  definite  source  of  light  is  diminished 
to  a  much  greater  extent  in  passing  through  a  layer  of  the  reacting 
gases  than  it  is  when  the  light  is  allowed  to  pass  through  an 
equivalent  layer  of  pure  chlorine.  Since  the  absorption  due  to  the 
admixed  hydrogen  is  negligibly  small,  it  is  apparent  that  the  photo- 
chemical change,  which  occurs  in  the  mixed  gases,  is  accompanied 
by  the  absorption  of  light  energy.  This  transformation  of  light 
energy  into  chemical  energy  may  be  regarded  as  the  distinguishing 
characteristic  of  all  photo-chemical  reactions. 

From  the  data  obtained  in  the  experimental  investigation  of 
a  number  of  such  reactions,  it  appears  that  these  are  in  general 
imimolecular,  and  are  distinguished  from  reactions  which  are  not 
light-sensitive  by  the  relatively  small  influence  which  an  alteration 
of  temperature  has  on  the  velocity  with  which  they  take  place. 
These  facts  have  led  to  the  view  that  the  absorbed  radiant  energy  is 
not  directly  responsible  for  the  chemical  change,  but  that  its  action 
consists  in  a  preliminary  transformation  of  the  reacting  system. 
This  change,  which  may  consist  in  the  intramolecular  transformation 
of  the  molecules  of  the  light-absorbing  substance,  or  in  the  formation 

1  Bngnrsxky,  Zeit.  physik.  Chem.,  1901,  38,  561. 

2  Ann.  Phijsik,  1857,  101,  251. 


PHOTO-CHEMICAL  REACTIONS  323 

of  molecular  complexes  which  act  as  reaction  nuclei,1  is  then  followed 
by  the  chemical  reaction  proper,  and  if  the  speed  of  the  latter  is 
relatively  very  large  it  is  obvious  that  the  rate  of  formation  of  the 
products  of  the  photo-chemical  change  will  be  determined  by  the 
speed  at  which  the  preliminary  light  change  occurs. 

If  the  system  in  which  the  photo-chemical  reaction  occurs  is 
homogeneous,  then,  according  to  Nernst,2  the  velocity  of  the  reaction 
at  any  moment  will  be  given  by  the  ordinary  kinetic  equation 


in  which  a,  6,  ...  c,  d  ...  are  the  concentrations  of  the  reacting  sub- 
stances, m,  w,  ...p,q...  the  number  of  molecules  of  the  several 
substances  actually  involved  in  the  change,  and  k  and  V  are  the 
velocity  coefficients  of  the  two  opposed  reactions.  The  values  of 
7c  and  fc'  depend  on  the  intensity  of  the  light  acting  on  the  system, 
nnd  for  light  of  the  same  kind  are,  in  certain  cases  at  any  rate, 
proportional  to  the  intensity.  In  consequence  of  absorption,  the 
light  intensity  varies  from  point  to  point  of  the  reaction  mixture, 
with  the  result  that  differences  in  concentration,  due  to  the  varying 
reaction  velocities,  occur,  which  can  only  be  equalised  by  the  opera- 
tion of  diffusion  or  by  mechanical  mixing.  On  this  account,  it 
is  evident  that  the  velocity  coefficients  which  are  obtained  in  any 
series  of  experiments  can  only  represent  average  values,  which  are 
influenced  by  the  particular  conditions  under  which  the  reaction 
is  allowed  to  take  place. 

Although  in  the  case  of  certain  non-reversible  changes  the 
experimental  observations  of  the  rate  of  change  appear  to  be  in 
satisfactory  agreement  with  the  above  general  equation,  it  is  im- 
probable that  this  can  be  regarded  as  the  expression  of  the  funda- 
mental law  of  photo-kinetics.  According  to  Luther  and  Weigert,3 
the  ordinary  dynamic  equation  is  certainly  not  applicable  to  re- 
versible photo-chemical  changes,  and  these  authors  formulate  the 
fundamental  Lvar  in  the  following  words  —  '  the  quantity  of  a  substance, 
sensitive  to  light,  which  undergoes  change  in  a  given  element  of 
volume  per  unit  of  time,  is  proportional  to  the  light  absorbed  during 
the  same  time  by  the  substance  contained  in  this  volume  element.' 

This  quantitative  statement  is  obviously  one  which  refers  only  to 
the  primary  reaction  in  which  the  light  rays  are  directly  involved, 
and  does  not  necessarily  determine  the  rate  of  formation  of  the  final 

1  Cf.  Weigert,  Ann.  Physik,  1907  (iv),  24,  243. 

2  TheoretiscJte  Chemie,  Sixth  Edition,  trans,  by  H.  T.  Tizard,  1911. 
s  Zeit.  physik.  Mem.,  1905,  51,  297;  1905,  53,  385. 

Y    2 


324  DYNAMICS  OF  ORGANIC  REACTIONS 

products  of  the  photo-chemical  change,  for  the  rate  at  which  these 
are  produced  will  be  influenced  by  the  relative  speeds  of  the  primary 
light  change  and  any  subsequent  change  or  changes  of  a  non-photo- 
chemical character.  The  velocity  of  these  subsequent  changes  will 
of  course  be  regulated  by  the  operation  of  the  mass  law  as  expressed 
in  the  above  general  equation  (p.  822). 

As  an  example  of  a  reversible  photo-chemical  change  which  has 
been  examined  in  detail,  the  polymerisation  of  anthracene  will  be 
considered. 

Anthracene  ;r±  Dianthracene.  It  was  observed  by  Fritzsche l 
that  a  benzene  solution  of  anthracene  deposits  an  insoluble  poly- 
meric substance  when  exposed  to  sunlight.  Orndorff  and  Cameron 2 
showed  that  this  substance  is  dianthracene,  which  is  produced 
according  to  2C14H10  — »  C28H20 .  According  to  Luther  and  Weigert,3 
the  change  is  reversible,  depolymerisation  taking  place  in  the  absence 
of  light,  and  in  consequence  of  the  opposed  reactions  a  definite  state 
of  equilibrium  is  established  when  a  solution  of  anthracene  (or 
dianthracene)  is  exposed  to  light  for  a  sufficient  length  of  time.  The 
equilibrium  condition  is  dependent  on  the  nature  and  intensity  of 
the  light  rays,  the  nature  of  the  solvent,  the  temperature,  and  also 
the  concentration  of  the  solution. 

According  to  the  results  obtained  in  experiments  with  anisole  and 
phenetole  solutions  at  temperatures  between  150°  and  170°,  the 
depolymerisation  of  dianthracene  is  a  unimolecular  change,  the 
velocity  of  which  is  the  same  in  the  presence  or  absence  of  light.  In 
the  dark  it  proceeds  to  completion,  and  its  velocity  is  increased  in 
the  ratio  of  2-8  : 1  by  a  rise  of  temperature  of  10°  C.  On  the  other 
hand,  the  polymerisation  of  anthracene  is  dependent  on  the  absorption 
of  light  energy,  and  the  velocity  with  which  this  change  occurs  in 
a  given  solvent  and  at  a  definite  temperature  is  dependent  on  the 
nature  and  intensity  of  the  light,  the  extent  of  the  surface  exposed 
to  the  light  rays,  and  the  volume  of  the  solution,  but  is  independent 
of  the  concentration  of  the  anthracene.  As  in  the  case  of  most 
photo-chemical  reactions,  the  temperature  coefficient  is  very  small, 
a  rise  of  10°  C.  increasing  the  velocity  only  in  the  ratio  1-1:1. 

In  accordance  with  the  above  facts,  the  rate  of  progress  of  the 
photo-chemical  change  can  be  represented  by  the  equation 

dx/dt  =  fy-Js'x,        (1) 

1  J.  prakt.  Chem.,  1866,  101,  337  ;  1869,  106,  274. 

2  Amer.  Chem.  Journ.,  1893,  17,  658. 

•  loc.  cit. 


ANTHRACENE  ^±  DIANTHRACENE  325 

in  which  x  is  the  concentration  of  the  dianthracene  at  any  moment, 
&'  the  velocity  coefficient  for  the  reaction  C28H20  —  >  2C14H10  which 
is  independent  of  the  incident  light,  and  Jct  a  quantity  characteristic 
of  the  reverse  change  2G14H10  —  *  C28H20  which  is,  moreover,  pro- 
portional to  the  intensity  of  the  absorbed  light  and  the  area  of  the 
light-absorbing  surface,  and  inversely  proportional  to  the  volume 
of  the  reaction  mixture. 

If  X0  is  the  dianthracene  concentration  at  the  commencement  and 
£  =  Ui/k'  the  corresponding  equilibrium  value,  then,  by  integration, 
we  obtain  i  t  _ 


or,  if  the  solution  contains  no  dianthracene  at  the  start,  that  is, 
if    x0  =  0,     then 


The  following  table  shows  the  approximate  constancy  of  k'  during 
the  progress  of  the  reaction,  the  data  given  being  the  results  of  an 
experiment  in  phenetole  solution  at  167°. 

t  (minutes}  Anthracene  (millimoln  per  litre}  x  k' .  10* 

0  37-2 

125  31-8  2-71  32-2 

225  29-4  3-90  29-0 

370  27-1  5-07  26-4 

450  25-5  5-87  28-4 

565  24-3  6-45  27-9 

790  23-0  7-11  26-3 

£  =  8-12 

From  an  examination  of  all  the  observations  relating  to  the  photo- 
chemical change,  it  may  be  inferred  that  dianthracene  is  not  an 
immediate  product  of  the  light  action,  and  Luther  and  Weigert 
suppose  that  intermediate  photo-chemically  sensitive  substances 
are  formed.  If  this  assumption  is  made,  then  all  the  facts  can  be 
satisfactorily  interpreted  on  the  basis  of  one  or  other  of  the  two 
following  schemes,  in  which  A  =  anthracene,  D  =  dianthracene, 
Al  =  i  photo-anthracene  '  and  D1  —  i  photo-dianthracene  '. 

(1)  A  +  light  -»  Al ;  2Al-^D 

slow  rapid 

t 


slow 

(2)  A  +  light  ^±  Dl ;  Dl  -»  D 

i  nstantaneous  slow 


slow. 


326  DYNAMICS  OF  ORGANIC  REACTIONS 

Catalysed  Reactions.  The  velocities  of  many  organic  reactions 
are  greatly  accelerated  by  the  addition  of  substances  which  appear 
to  have  no  other  effect  than  that  of  increasing  the  speed  of  the 
change.  Acids  and  bases  are  the  most  generally  active  substances 
of  this  character. 

The  view  usually  accepted  in  regard  to  such  catalysed  reactions 
is  that  the  catalyst  forms  an  addition  compound  with  one  or  other 
of  the  original  reacting  substances,  and  that  the  subsequent  decom- 
position of  this  intermediate  substance  liberates  the  catalyst  and 
yields  simultaneously  the  products  of  the  chemical  change.  Evidence 
in  support  of  this  view  has  been  obtained,  not  only  in  the  case  of 
the  simple  catalysts  like  the  acids  and  bases,  but  also  from  a  study  of 
reactions  in  which  enzymes  play  a  corresponding  part  (Part  III, 
chap.  65). 

In  those  cases  in  which  the  role  of  the  catalyst  consists  in  the 
formation  of  intermediate  compounds,  it  is  evident  that,  from 
a  dynamical  standpoint,  we  have  to  deal  with  reactions  which 
occur  in  consecutive  stages,  and  that  the  phenomena  of  catalysis 
will  therefore  be  determined  to  some  extent  by  the  relative  speeds 
of  the  successive  changes  in  which  the  catalyst  is  involved. 

Influence  of  Solvent  on  Reaction  Velocity.  The  speed  of 
a  given  reaction  not  only  depends  on  the  active  masses  of  the  reacting 
substances  and  on  the  temperature,  but  varies  in  a  marked  manner 
with  the  medium  in  which  the  reacting  substances  are  dissolved. 
This  solvent  influence  cannot  be  referred  to  catalytic  action,  for  in 
the  case  of  reversible  changes  it  has  been  shown  that  the  state  of 
equilibrium  differs  considerably  according  to  the  solvent,  whereas 
a  true  catalyst,  in  consequence  of  the  equality  of  its  accelerating  effects 
on  the  opposed  reactions,  would  be  without  influence  on  the  final 
condition  of  the  system. 

In  the  investigations,  which  have  had  for  their  particular  goal 
the  elucidation  of  the  influence  of  the  medium,  organic  reactions 
have  been  almost  exclusively  examined.  The  data  in  the  following 
table  suffice  to  show  that  the  influence  of  the  solvent  on  the  speed  of 
chemical  change  is  not  determined  by  the  specific  character  of  the 
solvent,  for  the  order  of  the  solvents,  when  tabulated  according  to 
the  velocities  of  one  reaction,  is  in  general  quite  different  from  the 
order  obtained  when  a  second  reaction  is  made  the  basis  of  com- 
parison. 

Under  I  are  given  the  relative  velocities  for  the  reaction  between 
triethylamine  and  ethyl  iodide  at  1000,1  under  II  corresponding 

1  Menschutkin,  Zeit.  physik.  Chem.,  1800,  C,  41. 


INFLUENCE  OF  SOLVENT  ON  REACTION  VELOCITY  327 

numbers  for  the  inversion  of  menthone  at  200,1  and  under  III  the 
values  for  the  conversion  of  the  syn-form  of  anisaldoxime  into  the 
anti-form  at  26°.2 

Solvent.  I.  II.  III. 

Methyl  alcohol  2-87  1-00  2-07 

Ethyl  alcohol  2-03  2-60  1-86 

Isobutyl  alcohol  1-43  4-64  0-96 

Allyl  alcohol  2-40  0-63  1-56 

Benzyl  alcohol  7-42  0-37  3-1 4 

Benzene  0-38  3-13 

Xylene  0-16  2-34 

He*ane  0-01 

That  the  influence  of  the  solvent  on  the  speed  varies  very  con- 
siderably according  to  the  nature  of  the  reaction  is  also  shown  by 
a  comparison  of  the  quantities  of  the  two  sets  of  products,  which  are 
formed  when  two  concurrent  reactions  give  rise  to  the  formation  of 
isomeric  substances,  as  in  the  case  of  the  action  of  bromine  on  the 
homologues  of  benzene.  Broinination  experiments  have  been  carried 
out  by  Brunei*  and  Vorbrodt,8  in  which  the  hydrocarbon  was  diluted 
with  three  times  its  volume  of  the  solvent  to  be  examined  and  the 
reaction  mixture  kept  in  the  dark  at  25°.  The  numbers  in  the 
following  table,  which  give  the  fraction  of  the  total  reacting  bromine 
which  enters  the  side-chain,  show  clearly  that  the  distribution  of 
bromine  between  side-chain  and  nucleus  is  very  largely  dependent  on 
the  solvent,  and,  since  this  distribution  is  determined  by  the  relative 
velocities  of  the  concurrent  reactions,  it  follows  that  the  influence 
of  the  solvent  on  the  speed  varies  considerably  according  to  the 
particular  chemical  change,  even  when  very  similar  reactions  only 
are  considered. 

Solvent.  Toluene.    Ethyl  benzene.     0-Xylene.      p-JTylene.       m-Jfylene. 

CS3  0-851  1-0                 —                 0-89 

CC14  0-566                                 0-42                 0-63                0-03 

C6H6  0-355  0-90                                   0-41                0-01 

CHCI,  —  0-63 

CH3.C02H  0-OA  0-27                                                            — 

C6H5CN  0-22 

C6H5NOa  0-027  0-15            0-026               0-02 

It  has  been  supposed  that  the  velocity  differences  are  attributable 
to  differences  in  the  ionising  power  of  the  various  solvents,  and  in 
support  of  this,  it  has  been  pointed  out  that  there  is.  in  certain  cases, 
a  parallelism  between  the  reaction  velocities  and  dielectric  constants 
of  the  solvent  media.  The  view  that  this  is  the  determining  factor 

i  Tubandt,  Annalen,  1907,  354,  259. 

51  Patterson  and  Montgomerie,  Trans.  Chem.  Soc.,  1912,  101,  26. 

>  Butt.  Acad.  Sci.  Cracow,  1909,  221. 


328  DYNAMICS  OF  ORGANIC  REACTIONS 

cannot  be  entertained  very  seriously,  however,  in  view  of  the  very 
different  results  obtained  in  the  investigation  of  different  reactions. 

Although  in  certain  groups  of  solvents  there  is  some  evidence 
that  different  reactions  are  influenced  in  a  uniform  manner  by 
the  solvent,  yet,  on  the  whole,  the  relationships  appear  to  be  so 
erratic  that  it  seems  quite  plausible  to  suppose  that  the  differences 
are  due  to  the  formation  of  more  or  less  stable  compounds  between 
the  reacting  substances  and  the  solvents  in  which  they  are  dis- 
solved. 

According  to  van  't  Hoff,  the  velocity  of  transformation  of  a  sub- 
stance in  different  solvents  is  connected  with  the  solubility  of  the 
substance  in  these  media,  and  evidence  in  support  of  such  a  relation- 
ship has  been  recently  obtained  by  Dimroth.1 

Further  experimental  work  is  necessary,  however,  before  any 
definite  opinion  can  be  expressed  as  to  the  general  occurrence  of  such 
a  relationship. 

Heterogeneous  Reactions.  In  the  foregoing  consideration  of 
the  kinetics  of  chemical  changes  it  has  been  assumed  that  the 
system,  in  which  the  reacting  substances  are  contained,  is  homo- 
geneous. A  brief  reference  may  now  be  made  to  the  case  where  the 
reacting  substances  are  brought  together  in  different  states  of 
aggregation,  as  in  the  action  of  gases  on  liquids,  of  liquids  on  solids 
or  other  liquids,  &c.  In  general,  such  heterogeneous  reactions  involve 
a  succession  of  changes,  each  of  which  is  associated  with  a  time  factor, 
as  in  the  case  of  the  homogeneous  consecutive  reactions  already 
considered. 

In  the  interaction  between  liquids  and  gases  or  solids,  the  actual 
chemical  process  occurs  in  the  liquid  phase,  and  the  chemical  change 
is  therefore  preceded  by  a  physical  process,  viz.  the  dissolution  of  the 
gas  or  solid  in  the  liquid. 

The  rate  at  which  the  final  products  are  formed,  as  represented 
by  a  velocity-time  curve,  will  therefore  depend  on  the  relative 
speeds  of  the  consecutive  physical  and  chemical  changes.  If  the 
chemical  reaction  is  of  high  speed,  the  rate  of  progress  of  the  change 
will  be  determined  by  the  velocity  of  the  dissolution.  On  the  other 
hand,  if  the  chemical  change  is  relatively  slow,  and  arrangements 
are  made  whereby  the  gas  or  finely  divided  solid  is  maintained  in 
efficient  contact  with  the  liquid,  e.g.  by  a  suitable  shaking  apparatus, 
the  liquid  will  remain  in  a  condition  of  saturation  with  respect  to 
the  gas  or  solid  in  contact  with  it,  and,  so  far  as  the  succeeding 

1  Annalen,  1910,  377,  181. 


HETEROGENEOUS  REACTIONS  329 

chemical  change  is  concerned,  the  active  mass  of  the  dissolving 
substance  will  be  constant.  Where  the  dissolving  substance  is  a  gas, 
it  is  presumed  that  the  gas  pressure  is  constant,  as  would  be  the  case 
if  the  gas  were  bubbled  in  a  steady  stream  through  the  liquid. 
Under  these  circumstances  the  'order'  of  the  chemical  change  will 
be  the  determining  factor  so  far  as  the  form  of  the  velocity-time  curve 
is  concerned. 

Comparatively  few  organic  reactions  of  the  heterogeneous  type 
have  been  investigated  dynamically,  but  the  oxidation  of  the  gaseous 
hydrocarbons  by  a  solution  of  potassium  permanganate l  affords 
a  simple  example.  In  the  table  below  are  given  data  obtained  in  an 
experiment  in  which  methane  was  violently  agitated  with  excess  of 
a  five  per  cent,  solution  of  KMnO4. 

Period  of  agitation.         Volume  of  methane.  Volume  change. 

5  13-0 

10  12-7  0-3 

15  12-4  0-3 

20  12-1  0-3 

25  11-7  0-4 

30  11-4  0-3 

The  rate  of  oxidation  is,  according  to  these  numbers,  constant,  and 
the  observed  rate  of  change  is  probably  determined  by  the  velocity 
of  the  chemical  oxidation  process,  the  solution  being  maintained  in 
a  saturated  condition  by  reason  of  the  intimate  contact  between 
the  gas  and  the  solution  and  the  consequent  rapid  rate  at  which  the 
gas  dissolves. 

In  gas  reactions,  where  the  nature  and  extent  of  the  surface  of 
solids  in  contact  with  the  reacting  gases  have  been  shown  to  have 
a  large  influence  on  the  velocity  of  the  combustion  or  other  chemical 
change,  it  is  probable  that  successive  processes,  which  may  be 
grouped  under  the  head  of  heterogeneous  reactions,  are  frequently 
involved. 

REFERENCES. 

Studies  in  Cliemical  Dynamics,  by  J.  H.  van  't  Hoff  and  E.  Cohen.  Trans  by 
T.  Ewan.  Williams  and  Norgate,  1906. 

Chemical  Statics  and  Dynamics,  by  J.  W.  Mellor.  Text-books  of  Physical 
Chemistry.  Longmans,  1904. 

1  V.  Meyer  and  Saam,  Bo:  1897,  30,  1935. 


CHAPTER  V 

ABNORMAL  REACTIONS 

Steric  Hindrance.  From  time  to  time  curious  irregularities  have 
been  observed  in  the  progress  of  certain  typical  reactions.  These 
isolated  and  scattered  examples  have  now  been  correlated  and  traced 
to  one  fundamental  cause,  that  of  steric  hindrance.  The  term  is 
intended  to  denote  the  influence  exerted  on  a  reacting  group  by  the 
spatial  disposition  of  neighbouring  atoms.  The  choice  of  such  a 
term  is  unfortunate  since  it  connotes  a  theory  which,  though  appli- 
cable as  an  explanation  of  some  of  the  abnormal  reactions  considered 
in  this  chapter,  is  by  no  means  the  only  underlying  cause  and 
possibly  in  some  cases  not  the  cause  at  all. 

As  far  back  as  1872  Hofmann  found  that  dimethylxvlidine 
(CH3)2C6H3N(GH3)2,  dimethvlmesidine  fX^ff^VK^t  and 
pentamethylaminobenzene  (CH3)5C6.NH2  give  little  or  no  quaternary 
ammonium  compounds  when  heated  with  methyl  iodide  to  150°, 
and  concluded  that  '  this  inability  to  unite  with  methyl  iodide  must 
depend  upon  some  kind  of  molecular  arrangement  V  In  1883  Merz  A 
and  Weith2  found  that  perchloro-  and  perbromo-benzonitrile  and  hexa- 
chloro-a-naphthonitrile  cannot  be  hydrolysed  by  the  usual  reagents; 
and  in  the  following  year  Hofmann  made  the  same  observation  ' 
regard  to  tetramethyl-  and  pentamethyl-benzonitrile. 

CN  ON 

CH3/\CH 

H 

CH 

During  the  years  1891  and  1892,  in  a  more  extended  investigation, 
Glaus  and  his  pupils  showed  that  resistance  to  hydrolysis  is  greatly 
enhanced  if  one,  and  still  more,  if  both  ortho  positions  to  the  cyanogen 
group  are  substituted  by  halogen  alkyl  or  nitro  groups.3 

In  1889  Jacobson 4  noticed  that  pentamethylbenzamide 

C6(CH3)5CONH2 

(obtained   by  the    action   of    aluminium    chloride    on    a    mixture 
of  chloroformamide  and   pentamethylbenzene)    completely    resists 

*  Ber.,  1872,  5,  713,  718;  1875,  8,  61.  a  Ber.,  1883,  16,  2880,  2892. 

3  Annalen,  1891,  265,  378  ;  266,  225  ;  1892,  269,  212  et  seq. 

4  Ber.,  1889,  22,  1219. 


STERIC  HINDRANCE  831 

hydrolysis,  and  Glaus 1  again  pointed  out  that,  like  the  nitriles,  many 
diortho-substituted  derivatives  of  ^-toluylamide  exhibit  unusual 
stability. 

N02  N02 

/"     ~\CO.NH2 

N02  ___ 

•-Nitro-o-bromo-jj-toluylamide.  o-Dinitro-^-toluylamide.    fJ. 

Br 

CH3/~      \CO.NH, 

Br 

o-Dibromo-j>-toluylamide. 

Since  then  the  conditions  which  determine  the  hydrolysis  of  cyanides 
and  amides  have  been  made  the  subject  of  more  careful  study  by 
Sudborough  and  by  Remsen  and  Reid,  and  will  be  referred  to  again 
(p.  345).  In  1890  Pinner 2  observed  similar  anomalies  in  the  prepara- 
tion of  imino-ethers  from  nitriles  by  the  action  of  alcohol  and  hydro- 
chloric acid,  which  usually  takes  place  according  to  the  equation : 

2SSL 

R.CN-f  C2H5OH  +  HC1  =  R.  C<f  .  HC1 

XOC2H5 

Certain  ortho-substituted  nitriles  refused  to  react.  Neither  o-tolu- 
nitrile,  2*4  dirnethylbenzonitrile,  nor  a-naphthoic  nitrile  (which  may 
be  regarded  as  an  ortho-substituted  compound)  give  iniino  ethers, 
whereas  /?-naphthoic  nitrile  enters  readily  into  the  reaction. 

CN 


o-Naphthoic  nitrile.         0-Naphthoic  nitrile. 

And,  again,  both  cyanogen  groups  in  isophthalic  and  terephthalic 
nitrile  readily  react,  whereas  in  homophthalic  nitrile  only  one  cya- 
nogen group  forms  an  imino  ether. 


Homophthalic  nitrile. 

1  Annaltn,  1891,  265,  864  ;  266,  223  ;  1892,  260.  203. 
1  J5«r.,  1890,  23,  2917. 


332  ABNORMAL  REACTIONS 

Another  series  of  observations  belonging  to  the  same  class  of  pheno- 
mena was  the  subject  of  a  careful  study  by  Kehrmann  *,  who  found 
that  ortho  substitution  in  the  quinones  retards  or  inhibits  the  forma- 
tion of  oximes.  Quinone  gives  a  dioxime,  w-dichlorcquinone  yields 
a  monoxime,  and  chloranil  gives  none. 

C:NOH 


<J:NOH 

Quinonedioxime.  m-Dichloroquinoneoxime. 

In  the  case  of  mono-substituted  quinones,  such  as  monochloroquinone 
and  toluquinone,  the  oxygen  which  has  no  ortho  substituent  is  first 
replaced  by  the  oxime  group  before  the  second  oxygen  reacts. 

O 

;CHq 


0 


NOH 

In  the  case  of  para-disubstituted  quinones  containing  a  halogen  and 
a  methyl  group,  the  oxime  group  replaces  oxygen  in  the  ortho  posi- 
tion to  the  alkyl  group.  Where  two  alkyls  are  present  oxygen  is 
first  replaced  in  the  ortho  position  to  the  smaller  group.  Examples 
of  this  are  afforded  by  p-chlorotoluquinone  and  thymoquinone. 


II 
NOH 

Kehrmann  concluded  that  it  is  less  the  nature  of  the  substituents 
(halogen  or  alkyl)  than  their  presence  in  the  ortho  position  to  the 
quinone  oxygen  which  interferes  with  the  reaction. 

Similar  irregularities  have  frequently  been  observed  in  the  forma- 

1  Ber.,  1888,  21,  8315 ;  1890,  23,  8557  ;  J.  prakt.  Chetn.,  1889  (2),  40,  257;  1890 
(2),  42,  134 ;  see  also  Nietzki  and  Schneider,  Ber.,  1894,  27,  1431. 


STERIC  HINDRANCE  333 

tion  of  oximes  from  aromatic  ketones.     Neither  phenylmesitylketone, 
xylyl-o-tolylketone  nor  benzpinacoline  react  with  hydroxylamine.1 


CH3 


Hr 


CO 

C 

Benzpina- 

Phenylmesityl-  coline. 

ketone. 

Xylyl-o-tolylketonc. 

Many  examples  of  the  same  kind  have  been  recently  brought  to 
light  by  Baum  and  V.  Meyer.2  It  should,  however,  be  pointed  out 
that  the  nature  of  the  second  radical  attached  to  the  ketone  group 
also  influences  the  result,  for  both  mesityl  aldehyde  and  mesityl- 
glyoxylic  ester  readily  form  oximes. 

CIL 


CHO 

Mesityl  aldehyde.  Mesitylglyoxylic  ester. 

From  the  close  analogy  existing  in  structure  and  mode  of  formation 
between  the  hydrazones  and  oximes,  similar  results  might  be  looked 
for  in  the  action  of  phenylhydrazine,  an  anticipation  which  experi- 
ence has  fully  justified.  The  presence  of  ortho  substituents  retard 
or  prevent  the  reaction  in  precisely  the  same  way.  On  the  other 
hand  mesitylglyoxylic  acid,  and  especially  its  dinitro  derivative, 
unite  with  this  reagent.3 

A  further  example  of  interference  is  afforded  by  the  well-known 
reaction  between  aromatic  aldehydes  and  primary  aromatic  amines, 
which  give  rise  to  benzalanilines.  Hantzsch  found  that  the  reaction 
does  not  occur  with  symmetrical  tribromo-  and  trinitro-aniline.4 

1  Hantzsch,  Bar.,  1890,  23,  2773 ;  Smith,  Bet:,  1891,  24,  4050  ;  Beckmann  and 
Wegerhoff,  Annalen,  1889,  252,  14  ;  Harries  and  Hubner,  Annalen,  1897,  296,  301. 

2  Ber.,  1895,  28,  3207 ;  1896,  29,  836,  2564. 

3  Annalen,  1891,  264,  144.  *  Ber.,  1890,  23,  2776. 


334  ABNORMAL  REACTIONS 

Furthermore,   the  formation  of  hydrazones   of  benzaldehyde  with 
ortho-substituted  hydrazines,  such  as  o-hydrazinebenzoic  acid, 

C6H4(COOH)NHNH2 

is  prevented,  whilst  the  corresponding  meta-compound  readily  com- 
bines. 

Victor  Meyer's  Esterification  Law.  The  majority  of  the  fore- 
going isolated  examples  of  abnormal  reactions  were  known  when, 
in  1894,  V.  Meyer  drew  attention  to  a  very  remarkable  case  of  inter- 
ference in  the  formation  of  esters,  which  has  found  expression  in 
his  esterification  latv. 

In  attempting  to  prepare  the  methyl  ester  of  mesitylene  carboxylic 
acid  by  the  action  of  hydrochloric  acid  on  a  mixture  of  alcohol  and 
acid  in  the  cold,  no  ester  was  formed,  although  the  same  process 
produced  a  nearly  theoretical  yield  in  the  case  of  benzoic  and  its 
monomethyl,  3 : 5-dimethyl  (mesitylenic  acid)  and  3:4:  6-trimethyl 
(durylic  acid)  derivatives.1  This  did  not  arise  from  any  inability 
on  the  part  of  mesitylene  carboxylic  acid  to  form  an  ester,  for  it  was 
readily  obtained  from  the  silver  salt  by  the  action  of  the  alkyl  iodide. 
This  observation  was  followed  by  the  discovery  that  durene  carboxylic, 
isodurene  carboxylic,  and  pentamethyl  benzoic  acid,  all  of  which 
contain  methyl  groups  in  both  ortho  positions  to  the  carboxyl,  share 
the  property  with  mesitylene  carboxylic  acid  in  yielding  no  ester  with 
hydrochloric  acid  in  the  cold. 


COOH  >v  .. 

CH /\CH3  CHs|        |°H3  CH3|        jCHa 

CH3I     JoHg  CH3XxJ 

XX  ^1W  CH, 


3  3 

Durene 

carboxylic  acid.  Isodurene  Pentamethyl 

carboxylic  acid.  benzoic  acid. 

The  same  thing  was  found  to  occur  with  diortho-substituted  chloro-, 
bromo-,  and  nitro-benzoic  acids,  which  formed  no  ester,  whilst 
similar  compounds  with  at  least  one  free  ortho  position  yielded  the 
ester  without  difficulty. 

That  the  inactivity  of  the  ortho-substituted  acids  arises  from  the 
position  occupied  by  the  groups  rather  than  from  their  chemical 
nature,  is  evident  from  the  similar  effect  produced  by  both  positive 

1  Ber.,  1894,  27,  510,  1580 ;  1895,  28,  1255,  2774,  3197 ;  see  also  Gattermaan. 
Per.,  1899,  32,  1117. 


VICTOR   MEYER'S  ESTERIFICATION  LAW          385 

alkyl  and  negative  halogens  and  nitro  groups.  That  the  interference 
is  further  determined  by  steric  conditions  seems  probable  from  the 
behaviour  of  both  mesityl  acetic  and  mesityl  glyoxylic  acid  (in  which 
the  carboxyl  is  removed  from  the  proximity  of  the  two  methyl 
groups),  for,  unlike  mesityl  carboxylic  acid,  they  readily  yield  esters. 

COOH 


CH2 


CH3 

These  prelim inaiy  observations  led  V.  Meyer  and  his  pupils  to 
a  more  elaborate  quantitative  examination  of  the  phenomenon.  In 
estimating  the  amount  of  ester  formed  at  a  given  temperature  they 
adopted  the  method  of  Fischer  and  Speier,  which  consists  in  heat- 
ing a  1  per  cent,  solution  of  the  acid  in  methyl  alcohol  containing 
2  per  cent,  of  hydrogen  chloride  for  two  hours  in  a  thermostat.  In  this 
way  it  became  possible  to  determine  the  relative  rate  of  esterification 
in  cases  where  the  process  was  not  prevented,  but  merely  retarded. 

Kellas  l  estimated  the  relative  quantity  of  ester  of  ortho-,  meta-, 
and  para-isomers  of  mono-substituted  benzoic  acids  formed  at  different 
temperatures,  and  although  he  found  the  rate  of  esterification  to 
increase  with  rise  of  temperature,  the  ortho  compound  always  yielded 
the  smallest  amount  of  ester.  The  following  examples,  which  repre- 
sent the  percentage  of  acid  esterified  in  two  hours  at  51°,  illustrate 
the  point  in  question : 

CH,  Cl  Br  I  NO2 

o.  48-3  50-9  43-4  20-5  8-6 

MI.  77.1  72.0  66.6  57-6  67-1 

P-  75-6  705  61.0  52-9  57-1 

Benzoic  acid  =  82-5. 

The  results  agree  with  the  velocity  constants  (K)  of  esterification 
which  were  ascertained  by  Goldschmidt.2  The  reaction  between 
acid  and  alcohol  is  bimolecular,  but  if  the  quantity  of  alcohol  is 
large  in  proportion  to  the  acid,  the  former  may  be  regarded  as  con- 
stant in  quantity,  whilst  the  influence  of  the  small  amount  of  hydro- 
chloric acid  (2  per  cent.),  which  acts  the  part  of  a  catalyst,  is  too 
insignificant  to  be  regarded.  The  reaction,  therefore,  resolves  itself 

1  Zeit.  phys.  Chem.,  1897,  24,  221.  2  Ber.,  1895,  28,  3218. 


336  ABNORMAL  REACTIONS 

into  a  unimolecular  one,  and  the  velocity  constant  may  be  determined 
from  the  usual  equation  for  a  unimolecular  non-reversible  reaction, 

_       1  ,         a 
ft  =  7  log 


t     °  a—x 

in  which  k  is  the  velocity  constant,  t  the  time,  a  the  concentration 
of  the  acid  at  the  beginning,  and  x  the  amount  of  ester  formed  in 
time  t.  By  heating  at  constant  temperature  and  withdrawing  a  por- 
tion of  the  mixture  at  intervals,  the  quantity  of  ester  formed  can  be 
rapidly  estimated  by  titrating  the  free  acid.  The  following  are  some 
of  the  numbers  obtained  for  7c : 

CH3                     Br  N0a 

o.          0-0111                0-0203  0-0028 

m.          0-0470                0.0553  0-0296 

P.          0.0241                0-0450  0-0261 

Benzoic  acid  =  0-0428. 

Attention  is  drawn  to  the  fact  that  in  both  series  of  determinations 
the  effects  of  meta-  and  para-substitution  are  not  equivalent,  and  the 
greater  esterification  values  in  the  case  of  the  meta- compounds  points 
to  the  existence  of  other  factors  in  the  phenomenon  of  interference 
which  cannot  be  disregarded  in  seeking  for  a  complete  explanation. 
The  relative  amount  of  esterification  of  different  diortho  acids  has 
also  been  the  subject  of  a  careful  study  by  V.  Meyer.1  He  found, 
for  example,  that  no  esterification  took  place  in  twelve  hours 
at  0°,  or  by  Fischer  and  Speier's  method  in  the  case  of  thymotic, 
o-phenylsalicylic,  mesitylene  carboxylic,  and  other  diortho  acids  in 
which  both  ortho  hydrogen  atoms  are  replaced  by  hydroxyl  or  methyl 
groups ;  but  that  if  hydrochloric  acid  gas  is  passed  into  the  boiling 
alcoholic  solution  for  several  hours,  the  following  percentage  of  ester 

was  formed, 

Thymotic  acid  23-3 

o-Phenylsalicylic    „  76-5 

Mesitylene  carboxylic    „  64-5 

Pentamethyl  benzole    „  70 

Durene  carboxylic    ,,  60 

whereas  symmetrical  trichloro-,  tribromo-,  trinitro-,  and  2  : 6-dibromo- 
benzoic  acids  under  similar  conditions  remained  unchanged.  Van 
Loon  and  V.  Meyer 2  have  also  shown  that  2-fluoro-6-nitrobenzoic  acid 
gives  2  per  cent,  of  ester  on  standing  for  twelve  hours  at  0°,  that 
is,  under  conditions  which  in  the  case  of  benzoic  acid  yield  97  per 
cent,  of  ester,  whilst  V.  Meyer  found  that  even  the  ortho  hydrogen 
atoms  in  benzoic  acid  diminish  the  amount  of  ester,  inasmuch  as 

1  Ber.,  1895,  28,  1254.  a  Ber.,  1896,  29,  839. 


VICTOK   MEYER'S  ESTERIFICATION  LAW         337 

phenylacetic  acid  is  more  rapidly  esterified  than  benzoic  acid.  It 
would,  therefore,  appear  that  whilst  hydrogen,  fluorine,  hydroxyl,  and 
methyl  retard  esterification,  to  a  greater  or  less  extent,  it  is  only 
completely  arrested  by  chlorine,  bromine,  iodine,  and  nitro  groups. 
V.  Meyer  draws  the  conclusion  that  the  atomic  weights  or  size  of  the 
groups  which  prevent  esterification  in  the  hot  liquid  are  much  larger 
than  those  which  only  produce  this  effect  in  the  cold.1 

Retard.  Prevent. 

H  =    1  Cl  =    35-4 

CH3  =  15  N  \  =    46 

OH  =17  Br  =    80 

P  =  19  I  =  127 

This  view  cannot  be  strictly  maintained  ;  for  it  has  been  shown 
that  little,  if  any,  difference  is  effected  by  substituting  a  larger  alkyl 
radical  for  methyl,  and  moreover  there  is  little  doubt  that  in  spite  of 
its  comparatively  small  atomic  weight,  the  nitro  group  has  a  much 
more  powerful  effect  than  the  other  three  halogens  of  the  second 
column  in  preventing  esterification.* 

A  further  interesting  observation  on  the  rate  of  esterification  is  the 
effect  produced  by  an  adjoining  nucleus.  From  the  fact  that  both 
/3-chloro-  and  /?-hydroxy-a-naphthoic  acid  cannot  be  esterified  in  the 
cold, 

COOH  COOH 


whereas    /2-chloro-    and    /?-hydroxy-/?-naphthoic    acid    behave    like 
benzoic  acid, 


COOH 


it  follows  that  the  CH  group  of  the  adjoining  nucl  us  behaves  like 
an  ortho  substituent.8 

The  effect  of  ortho  carboxyl  groups  on  the  rate  of  esterification 
appears  from  the  behaviour  of  the  polycarboxylic  acids  to  resemble 


1  Ber.,  1895,  28,  12GO.  »  Kellas,  Zeit.  phys.  Chem.,  1897,  24,  221. 

3  Ber.,  1895,  28,  1254. 
IT.  I 


338  ABNORMAL  REACTIONS 

generally  that  of  the  other  groups.1    Whilst  trimesic  and  pyromellitic 
acid  give  a  nearly  quantitative  yield  of  neutral  ester  in  the  cold, 

COOH 

COOH/^COOH 


HOOcl     JO 


v/OOH  COOH'       'COOH 

Trimesic  acid.  Pyromellitic  acid. 

hemimellitic  and  prehnitic  acid  give  a  dimethyl  ester. 


COOCH3  COOCH3 


I     JcOOCH3  .Jc 


OOH 
COOCH3 

Hemimellitic  ester.  Prehnitic  ester. 

In  boiling  alcohol,  however,  prehnitic  acid  gives  a  neutral  ester. 

The  following  two  dibasic  acids  give  respectively  neutral  and  acid 
esters  :  2 

CH3  COOH 

CH3OOC/\COOCH3 


COOCH3 

Neutral  ester.  Acid  ester. 

3-Nitro-  and  4  :  6-dinitrophthalic  acids  yield  chiefly  monoalkyl  esters, 


X,COOCH3 
JCOOH 


!coocH3 

3-Nitrophthalic  ester.  4  : 6-Dinitrophthalic  ester. 

whilst  3 : 6-dinitrophthalic  acid,  the  tetrahalogen  derivatives  of  tere- 
phthalic  and  isophthalic  acid  and  also  mellitic  acid  form  no  ester 
at  all.3 

1  Ber.,  1894,  27,  1580. 

2  Jannasch  and  Weiler,  Ber  ,  1895,  28,  531. 

3  Ber.,  1894,  27,  3146 ;  1895,  28,  3197. 


VICTOR  MEYER'S  ESTERI  FIG  ATION  LAW  339 

N02  COOII         COOH  COOH 

.COOH          x/'Nsx      X*  HOOC/\COOH 


)OH         xx      x        COOH         HOOC,       COOH 


HOOC,      JC 


N02  COOH         X  COOH 

3  :  6-Dinitrophthalic      Tetrahalogen  (X)  derivatives  Mellitic  acid. 

acid.  of  torephthalic  and  isophthalic 

acid. 

On  the  other  hand,  the  tetrahalogen  derivatives  of  phthalic  acid 
and  3  :  6-dichlorophthalic  acid,  as  well  as  3  :  6-dichloro-2-benzoyl- 
benzoic  acid  and  tetrachloro-2-benzoylbenzoic  acid  l  do  not  obey  the 
esterification  law,  inasmuch  as  they  form  monoalkyl  esters.  Another 
exception  is  the  3-nitrophthalic  acid,  which,  according  to  Marckwald 
and  McKenzie,2  forms  with  amyl  alcohol  a  little  a-monoamyl  ester 
in  addition  to  the  /^-compound,  but  if  the  anhydride  of  the  acid  is 
heated  with  the  alcohol,  it  is  the  a-ester  which  is  formed.  This 
is  true  of  a  large  number  of  alcohols,3  and  has  received  no 
explanation. 

N02  NO2 

,/NcooR 


L    JCOOR  i    JCOOH 

/3-ester.  o-ester. 

Also  hemipinic  acid,  which  forms  an  acid  ester  in  the  first  instance, 

OCH3 


JOOH 
>OCH3 

Hemipinic  monomethyl  ester. 

can  be  converted  by  prolonged  esterification  into  the  neutral  com- 
pound.4 

Among  the  hydroaromatic  acids  it  is  a  significant  fact  that 
whereas  hydromellitic  acid  forms  no  ester,  the  stereoisomeric  iso- 
hydromellitic  acid  forms  a  monoalkyl  ester,  the  difference  being  no 
doubt  due  to  a  difference  in  the  space  configuration  of  the  carboxyl 

1  Graebe,  Ber.,  1900,  33,  2026.  »  Ber.,  1901,  34,  486. 

3  McKenzie,  Trans.  Chem.  Soc.,  1901,79,  1135;  Cohen,  Woodroffe  and  Anderson, 
Trans.  Chem.  Soc. 
*  Wegscheider,  Monatsh.,  1895,  16,  137. 

z  2 


340  ABNORMAL  REACTIONS 

groups  round  the  ring.  One  may  suppose  that,  in  the  first  case,  the 
carboxyl  groups  are  all  on  the  same  side  of  the  molecule  and,  in  the 
second,  that  one  group  is  reversed  (Part  II,  p.  260). 

We  may  conclude  then  that  the  carboxyl  or  carbalkoxyl  group,  in 
spite  of  its  atomic  weight,  resembles  the  members  of  the  alkyl  and 
hydroxyl  series,  rather  than  those  of  higher  atomic  weight,  seeing 
that  its  effect  is  to  retard  rather  than  prevent  esterification. 

From  the  results  of  the  above  investigation  V.  Meyer  formulated 
the  following  law :  '  When  the  hydrogen  atoms  in  the  two  ortho 
positions  to  the  carboxyl  in  a  substituted  benzoic  acid  are  replaced 
by  radicals,  such  as  Cl,  Br,  N02,  CH3,  COOH,  an  acid  results 
which  can  only  be  esterified  with  difficulty  or  not  at  all.' 

Although  the  facts  ascertained  by  V.  Meyer  and  his  pupils  appear 
to  accord  very  well  with  the  theory  of  steric  hindrance,  it  must  be 
remembered  that  the  ester  law  is  only  applicable  to  a  particular  set 
of  conditions  in  which  a  catalyst  in  the  form  of  hydrogen  chloride 
is  used  and  that  the  mechanism  of  the  process  is  still  obscure. 
Rosanoff  and  Prager1  have  examined  the  formation  of  esters  of 
substituted  benzoic  acids- by  heating  the  acid  and  alcohol  together 
without  the  addition  of  a  mineral  acid  and,  contrary  to  Meyer's 
experience,  they  find  that  'aromatic  acids  with  one  or  both  ortho 
positions  occupied  combine  with  alcohols  more  slowly  although  to 
no  less  extent  than  acids  otherwise  constituted '.  Similar  results 
have  been  obtained  by  Michael.2 

It  is  a  significant  fact,  already  mentioned,  that  whereas  3-nitro- 
phthalic  acid  when  esterified  with  a  catalyst  yields  mainly  the 
a-ester,  the  anhydride  when  heated  with  an  alcohol  gives  mainly  the 
/2-ester. 

The  Esterification  Law  applied  to  Fatty  Acids.  The  interest- 
ing results  which  have  been  derived  from  the  study  of  the  aromatic 
acids  suggested  a  similar  behaviour  on  the  part  of  substituted  fatty 
acids  which  possess  a  structure  analogous  to  the  diortho  compounds 
of  the  aromatic  series. 

COOH 

^  COOH  COOH 

XC/NCX  C  or. 


H 


I  I 

C 


1  Journ.  Amer.  Chem.  Soc.,  1908,  30,  1895. 
a  Ber.,  1909,  42,  310,  317. 


ESTERIFICATION  LAW  APPLIED  TO  FATTY  ACIDS  341 


In  other  words,  it  seemed  not  unlikely  that  di-  and  tri-substituted 
acetic  acids  would  be  influenced  by  the  esterification  law.  Men- 
schutkin  in  1878  l  showed  that  the  rate  of  esterification  of  the  mono-, 
di-,  and  tii-methyl  acetic  acids  rapidly  decreases  in  the  order  given 
when  alcohol  and  acid  are  heated  together  in  the  absence  of 
hydrogen  chloride  (autocatalysis  2).  Lichty,8  using  the  same  method, 
found  that  the  increase  in  the  number  of  chlorine  atoms  facilitated 
esterification.  The  subject  has  received  a  much  more  thorough 
treatment  at  the  hands  of  Sudborough  and  his  colleagues,4  who  have 
determined,  by  the  method  employed  by  Goldschmidt,  the  esterifica- 
tion constants  (p.  335)  of  a  long  series  of  substituted  acetic  acids  in 
presence  of  hydrochloric  acid.  The  following  are  the  results  obtained, 
in  which  E  stands  for  the  esterification  constant  for  ethyl  alcohol  at 
14-5°  and  K  for  the  dissociation  constant  determined  by  Ostwald  and 
others. 


Acid. 

Formula. 

T^ 

K. 

Acetic 

CHS.COOH 

3.661 

0.00180 

Prop  ionic 

CH2Me.COOH 

3.049 

0.00134 

Monochloracetic 

CH3C1.COOH 

2.432 

0.155 

Phenylacetic 

CH2Ph.COOH 

2.068 

— 

Bromacetic 

CH2Br.COOH 

1.994 

0.138 

lodacetic 

CH2I.COOH 

1.713 

0.075 

Isobutyric 

CHMe2COOH 

1.0196 

0.00144 

Trimethylacetic 

CMes.COOH 

0.0909 

0.000978 

Dichloracetic 

CHCla-COOH 

00640 

5.14 

Diphenylacetic 

CHPh2.COOH 

0.05586 

— 

Dibromacetic 

CHBr3COOH 

0.0510 



Trichloracetic 

CC1S.COOH 

0.0372 

121.0 

a-Bromisobutyric 

CMesBr.COOH 

0.0356 

— 

aa-Dibromopropionic 

CMeBr3COOH 

0.0242 

3.3 

Tribr  macetic 

CBr3COOH 

0.01345 

— 

The  experimental  evidence  clearly  indicates  that  the  rate  of 
esterification  is  retarded  in  proportion  to  the  number  and  size  of 
the  atoms  or  groups  introduced  into  the  acetic  acid  molecule,  and 
is  independent  of  the  strength  of  the  acid  as  determined  by  its 
dissociation  constant.  The  divergence  from  Lichty's  results,  who 
found  that  esterification  increased  with  the  strength  of  the  acid,  may  be 
due,  as  in  the  case  of  the  aromatic  acids,  to  the  presence  of  a  catalyst. 
Similar  influences  therefore  affect  the  esterification  of  both  fatty  and 
aromatic  acids.  Other  contributions  to  the  subject  of  esterification 

1  Annalen,  1879,  195,  334 ;  197,  193. 

2  It  also  falls  off  with  the  greater  complexity  of  the  alcohol,  the  tertiary  alcohols 
combining  less  readily  than  the  secondary,  and  the  latter  less  than  the  primary. 

3  Amer.  Chem.  J.,  1895,  17,  27  ;  1896,  18,  590. 

*  Trans.  Chem.  Soc.,  1899,  75,  467  ;  see  also  Gyr,  Ber.,  1908,  41,  4308. 


342  ABNORMAL  REACTIONS 

have  only  served  to  demonstrate  the  steric  effects  which  underlie  the 
process.  One  investigation  by  Sudborough  and  Lloyd  has  reference 
to  tmsaturated  acids  of  the  acrylic  series,  ot  the  formula  CHX :  CY. 
COOH  and  CXY:  CZ  .  COOH,1  all  of  which  can  exist  in  cis  and  trans 
configurations  (Part  II,  chap,  iv),  Cis  acids  of  both  the  above 
formulae  are  difficult  to  esterify  by  Fischer  and  Speier's  method, 
whilst  the  corresponding  trans  acids  are  readily  converted  into 
esters.  Sudborough  and  Roberts  also  found  that  saturated  acids  are 
much  more  readily  esterified  than  the  corresponding  unsaturated 
acids.2 

A  paper 3  by  Bone,  Sudborough,  and  Sprangling  on  the  esterifica- 
tion  of  the  mono-esters  of  the  methyl  succinic  acids  '  affords  another 
example  of  the  retardation  induced  by  the  successive  introduction  of 
methyl  groups '.  Also,  Blaise 4  has  shown  that  in  as-diniethylsuc- 
cinic  acid  the  tertiary  carboxyl  is  more  difficult  to  esterify  than  the 
primary  group. 

The  same  thing  occurs  with  camphoric  and  homocamphoric  acid  in 
which  the  tertiary  carboxyl  remains  almost  completely  uneste rifled.5 

CH2— C(CH3) .  COOH  CH2— C(CH3) .  COOH 


C(CH3)2 


CHa)s 


CH2— CH  .COOR  CH2  -  CH .  CH2 .  COOR 

Camphoric  ester.  Homocamphoric  ester. 

From  what  has  been  already  stated  of  the  absence  of  any  relation 
between  the  dissociation  constants  and  rate  of  esterification  (p.  341), 
it  is  clear  that  the  process  is  not  determined  by  the  presence  of  free 
ions,  and  there  are  many  other  facts  which  point  in  the  same  direc- 
tion. The  explanation  suggested  by  Wegscheider  6  assumes  that  the 
ester  formation  is  preceded  by  the  addition  of  a  molecule  of  alcohol 
and  acid, 

O  OT? 

RC*y  _L  TTOT?  T?     C*/  OtT 

.  U'  +  liUKi  =  K  .  ^<— U±l 

X)H  \OH 

from  which  water  is  then  removed. 


R.C^-OH  +R.C         +HO 
VOH 


1  Trans.  Cliem.  Soc.,  1898,  73,  81.  2  Trans.  CJum.  Soc.,  1905,  87,  1840. 

3  Trans.  Chem.  Soc.,  1904,  87,  534.  «  Compt.  rend.,  1898,  126,  753. 

5  Haller,  Compt.  rend  ,  1889,  100.  68,  112  ;  1892,  114,  1516. 

6  Monatsh.,  1895,  16,  148. 


ESTERIFICATION  LAW  APPLIED  TO  FATTY  ACIDS    343 

This  view  finds  some  confirmation  in  the  fact  that  whilst  benzoic 
ester  forms  an  additive  compound  with  sodium  methoxide,  mesity- 
lene  carboxylic  ester  does  not. 

It  is  easy  to  conceive  that  the  presence  of  large  groups  or  atoms 
in  the  neighbourhood  of  the  carboxyl  of  the  acid  molecule  would 
interfere  with  the  interaction  of  the  alcohol  molecule  by  preventing 
the  formation  of  the  additive  compound. 

An  apparent  contradiction  of  this  view  is  the  formation  of  acetals 
(by  the  action  of  aldehydes  on  alcohols  in  presence  of  hydrochloric 
acid)  which  was  studied  by  E.  Fischer  and  Giebe,1 

C6H5 .  CHO  +  2CH3OH  =  C6H5CH(OCH3)2  +  H2O 

for  ortho-substituted  aldehydes  like  2 : 5-dichloro-  and  2-nitro-3 : 6- 
dichloro-benzaldehyde  react  more  readily  than  the  unsubstituted 
compound  itself;  but  this  may  be  merely  an  example  ot  steric 
hindrance  neutralized  by  the  specific  effect  of  acidic  groups,  which, 
like  nitro  groups  in  the  hydrolysis  of  esters  (see  below),  and  of  ortho- 
substituted  cyanides  (p.  345) ;  in  the  reduction  of  nitro  compounds 
(p.  350)  and  in  the  formation  of  hydrazones,  assist  the  reaction. 

Hydrolysis  of  Esters.  If  the  esterification  law  is  based  on  steric 
hindrance,  similar  influences  might  be  expected  to  underlie  the  rate 
of  ester  hydrolysis.  Such  indeed  is  the  case,  although  there  are 
notable  differences  in  the  character  of  ester  formation  and  hydrolysis, 
to  which  attention  will  be  drawn.  The  rate  of  hydrolysis  of  mono- 
substituted  benzoic  esters  was  examined  first  by  V.  Meyer 2  and  then 
more  thoroughly  by  Kellas,3  who  found  that  substitution  in  the 
ortho  position  hinders  the  process  more  than  in  the  meta-  or  para- 
position;  but  whilst  methyl  in  the  two  latter  positions  retarded 
hydrolysis  as  compared  with  benzoic  ester,  the  presence  of  the  halogens 
and  still  more  of  the  nitro  group  increased  it,  so  that  the  absolute 
rate  of  hydrolysis  of  both  the  mono-halogen  and  mono-nitro  sub- 
stituted benzoic  esters  is  in  many  cases  greater  than  that  of  benzoic 
ester  itself.  But  as  a  rule  the  general  effects  of  ester  hydrolysis  run 
parallel  with  those  of  esterification,  and  in  most  cases  the  esterifica- 
tion law  enables  us  to  predict  the  result. 

Thus  the  ortho-substituted  esters  of  a-naphthoic  acid  are  more 
difficult  to  hydrolyse  than  those  of  the  /^-compound ;  in  the  mono- 
halogen  or  mono-nitroterephthalic  esters  the  ester  group  in  the  meta 
position  to  the  substituent  is  first  attacked  ;  the  same  happens  with 

1  Ber.,  1898,  31,  545.  2  Ber.,  1895,  28,  188. 

8  Zdt.  phys.  Chem.,  1897,  24,  243. 


344  ABNOKMAL  KEACTIONS 

the  nitrophthalic  esters,  in  which  hydrolysis  of  the  ester  group 
farthest  from  the  nitro  group  takes  precedence.  An  explanation  such 
as  V.  Meyer  applied  to  esterification  may  be  repeated  here,  for  the 
molecule  of  alkali  may  form  an  additive  compound  with  the  ester 
previous  to  the  rupture  of  the  alcohol  molecule. 

In  regard  to  the  aliphatic  acids  Reicher1  found  that  the  esters  of 
substituted  acetic  acids  and  secondary  and  tertiary  alcohols  are  more 
difficult  to  hydrolyse  than  those  of  normal  acids  and  alcohols. 
Sudborough  and  Feilmann,2  from  a  careful  investigation  of  ester 
hydrolysis,  concluded  that  two  factors  were  concerned  in  the  process, 
namely,  the  configuration  of  the  acid  as  determined  by  the  proximity 
of  radicals  to  the  carboxyl  group  and  the  strength  of  the  acid,  and 
that  these  two  factors  may  be  opposed  so  that  if  one  is  more 
prominent  the  effect  of  the  other  is  concealed. 

Hydrolysis  of  Amides  and  Acyl  Chlorides.  The  steric  influences 
which  retard  hydrolysis  appear  to  underlie  the  formation  or  non- 
formation  of  amides  when  ammonia  acts  on  esters,  and  the  same 
phenomenon  has  been  observed  in  the  hydrolysis  of  ortho  -substituted 
acid  chlorides,  cyanides,  and  amides,  as  well  as  in  the  action  of 
alcohols  on  acid  chlorides.  Fischer  and  Dilthey  studied  the  first 
reaction  in  the  case  of  the  series  of  alkyl  malonic  esters,3  whilst 
V.  Meyer,4  Sudborough  and  his  collaborators,  and  also  Glaus  investi- 
gated the  hydrolysis  of  acid  chlorides,  amides,  and  cyanides  of  the 
benzene  series.  Fischer  and  Dilthey  found  that  not  only  did  the 
presence  of  dialkyl  groups  in  malonic  ester  retard  the  formation  of 
amides,  but  that  diethyl  and  dipropylmalonamide  were  more  slowly 
hydrolysed  than  the  parent  substance.5  They  explain  the  inactivity 
of  the  dialkyl  malonic  esters  on  the  ground  that  unlike  the  monoalkyl 
derivatives  they  cannot  assume  the  active  tautomeric  form  repre- 
sented thus  : 

CO.OC2H5 


From  a  study  of  the  acid  chlorides  Sudborough  6  concludes  that 
those,  in  which  either  of  the  ortho  positions  are  substituted,  are 

1  Annalen,  1835,  228,  257  ;  1886,  232,  103;  1887,  238,  276. 

2  Proc.  Chem.  Soc.,  1897,  13,  241.  8  Ber.,  1902,  35,  844. 

4  Ber.,  1894,  27,  3153.  «  Ber.,  1902,  35,  852. 

6  Trans.  Chem.  Soc.,  1895,  67,  601. 


HYDROLYSIS  OF  AMIDES  AND  ACYL  CHLORIDES    345 

readily  decomposed  by  dilute  alkalis,  whereas  those  which  have 
a  bromine  atom  in  one  ortho  position  are  relatively  more  stable,  but 
where  both  ortho  positions  are  occupied  by  bromine  atoms  the  com- 
pounds are  remarkably  stable  and  are  only  converted  into  the  corre- 
sponding sodium  salts  of  the  acids  by  long-continued  boiling  with  an 
alkali  solution. 

It  has  already  been  mentioned  that  Glaus  and  his  pupils  in  1891 
and  1892  observed  the  difficulty  with  which  ortho-substituted  benz- 
amides  undergo  hydrolysis.  The  subject  attracted  fresh  interest 
after  the  discoveiy  of  the  ' esterification  law',  and  Sudborough,  in 
conjunction  with  Jackson  and  Lloyd,1  submitted  the  process  to  a 
more  searching  examination.  The  hydrolysis  was  effected  with  30, 
50,  or  75  per  cent,  sulphuric  acid  at  160°,  or  at  the  boiling-point,  and 
a  comparison  made  of  the  quantities  of  acid  formed  in  a  given  time. 
The  results  conclusively  showed  that  ortho-substituted  derivatives 
strongly  retarded  the  process,  so  that  under  conditions  which  effected 
almost  complete  hydrolysis  of  3  :5  and  2  :  4-dibromobenzamide  only 
11  per  cent,  of  2:6-dibromo  and  4-5  per  cent  of  2 : 4  :  6-tribromo- 
benzamide  were  converted.  Of  the  same  nature  are  the  constants 
obtained  by  Remsen  and  Reid 2  of  the  comparative  rates  of  hydrolysis 
of  ortho-,  meta-,  and  para-substituted  benzamides  in  which  the  re- 
tarding effect  of  the  ortho  substituent  is  very  evident. 

The  curious  observation  made  by  Fischer8  that  hydroxybenzoic 
esters  and  amides  (ortho  or  para)  are  more  easily  hydrolysed  when 
the  hydrogen  of  the  hydroxyl  group  is  replaced  by  methyl  can 
scarcely  be  due  to  steric  influence. 

Hydrolysis  of  Cyanides.  That  the  cyanides  should  behave  like 
amides  on  hydrolysis  is  a  natural  conclusion  which  the  observations 
of  Glaus  and  others  on  the  hydrolysis  of  substituted  benzonitriles, 
referred  to  in  the  earlier  part  of  the  present  chapter,  have  served  to 
confirm.  The  subject  is  reopened  merely  to  draw  attention  to  the 
influence  of  the  nitro  group  in  this  reaction,  for  it  is  not  a  little 
significant  that  the  presence  of  one,  still  more  of  two,  nitro  groups 
greatly  facilitates  hydrolysis.  Whilst  great  difficulty  is  experienced 
in  hydrolysing  sywm-trimethylbenzonitrile  the  mono-  and  dinitro- 
derivatives  may  be  completely,  though  slowly,  converted  into  acids.4 
It  is  clear,  therefore,  that  the  nitro  group  plays  a  special  role  in 


1  Trans.  Chem.  Soc.,  1895,  67,  601  ;  1897,  71,  229. 

8  Amer.  Chem.  J.,  1899,  21,  340. 

8  Ber.,  1898,  31,  3266. 

«  Kuster  and  Stallberg,  Annalen,  1894,  278,  207. 


346  ABNOKMAL  REACTIONS 

modifying  steric  influences,  a  fact  which  also  becomes  evident  in  the 
rate  of  reduction  of  nitro  compounds  (p.  350). 

Action  of  Alcohols  on  Acid  Chlorides.  Steric  influences  also 
determine  the  union  of  acid  chlorides  with  alcohols,  and  among  the 
series  of  menthyl  esters  of  disubstituted  benzoyl  chlorides  obtained 
by  the  writer  and  his  collaborators,1  it  was  invariably  found  that 
the  diortho  compound  requires  a  much  higher  temperature  and  more 
prolonged  heating  than  the  other  acid  chlorides  to  effect  combination 
with  menthol. 

Formation  of  Alky  la  mm  on  him  Iodides.  Reference  has  already 
been  made  to  Hofmann's  observation  that  certain  tertiary  aromatic 
amines  refuse  to  combine  with  alkyl  iodide  to  form  quaternary  com- 
pounds. The  subject  was  re-inves*tigated  by  Fischer  and  Windaus,2 
who  showed  that  it  was  clearly  the  eifect  of  steric  hindrance.  For  of 
the  six  isomeric  xylidines,  though  they  can  be  converted  into  tertiary 
bases  by  Noelting's  method  (using  methyl  iodide  and  sodium  carbon- 
ate), it  is  only  the  2  :  6-compound  which  gives  no  quaternary  ammo- 
nium iodide.  The  same  is  the  case  with  the  different  isomeric 
bromotoluidines  and  bromoxylidines.  Moreover,  Friedlander 3  found 
that  2  :  6-xylidine  can,  with  difficulty,  be  converted  into  the  tertiary 
diethyl  compound,  whilst  Effront  *  could  only  obtain  traces  of  the 
dimethyl  tertiary  base  with  2-methyl-6-isobutyl  toluidine  and  methyl 
iodide  at  150°.  Decker  drew  attention  to  the  same  phenomenon  in 
connection  with  the  o-  or  a-substituted  quinolines, 


0 

which,  like  the  diortho  xylidines  or  bromotoluidines,  will  not  combine 
with  alkyl  iodides. 

A  reaction  not  very  dissimilar  from  the  above  is  one  which  was 
examined  by  Scholtz  and  Wassermann.5  They  find  that  arylamines 
and  ae-dibromopentane  react  to  form  derivatives  of  piperidine. 

,CH2.CH2Br  CH2-CH2 

H2C<  +  H2NC6H5  =  H2C<  >NC6H5  +  2HBr 

\CH2 .  CH2Br  \H  _(<g2 

1  Trans.  Chem.  Soc.,  1906,  89,  1482.         3  Ber.,  1900,  33,  345,  1967. 

8  Monaish.,  1898,^9,  645.     «  Ber.,  1884,  17,  2317.     B  Ber.,  1907,  40,  852. 


FORMATION  OF  ALKYLAMMONIUM  IODIDES        347 

If,  however,  the  amine  is  substituted  in  the  ortho  position,  as  in 
o-toluidine    and    a-naphthylamine,   the    reaction    takes   a   different 
course  and  pentamethylene  diamines  are  formed  : 
EHN .  (CH2)5  .  NHR 

The  Alkylatioii  of  Bases  and  Phenols.  Decker1  found  that 
ortho  substituted  quinolines  will  not  combine  with  methyl  iodide, 
but  readily  react  with  methyl  sulphate.  The  latter  process,  how- 
ever, fails  with  a  number  of  diortho-substituted  bases.  In  the 
same  way  the  meta-  and  para-hydroxybenzoic  acids  can  be  alkylated 
with  ease  by  means  of  the  dialkyl  sulphates,  but  no  reaction  occurs 
with  salicylic  acid  or  with  a-  and  /?-hydroxynaphthoic  acids.2 

Acetylation  of  Secondary  Bases.  Paal  and  Kromschroder 3 
have  shown  that  not  only  does  o-nitrobenzyl  chloride  react  with 
difficulty  to  form  o-nitrobenzyl-o-nitraniline  when  the  m-  and  p- 
compounds  readily  unite,  but  that  the  product  obtained  is  proof 
against  acetylation. 


X Vy-LJ-r)  .   0.1  AA\ 

~~N02  NOa 

o-Nitrobenzyl-o-nitraniline. 

Furthermore,  of  the  compounds  obtained  by  combining  ^?-nitro- 
benzyl  chloride  with  the  three  isomeric  nitranilines,  only  the  o- 
nitraniline  derivative  resists  the  introduction  of  the  acetyl  and  formyl 
group.  It  follows  therefore  that  the  ortho-nitro  group  of  the  base 
controls  the  action,  and  from  the  fact  that  o-nitrobenzyl-o-anisidine 
gives  a  formyl  derivative,  it  would  seem  that  this  action  is  deter- 
mined by  the  negative  character  of  the  group. 

>— CH2.NH/ 

02  CH30~ 

o-Nitrobenzyl  o-anisidine. 

Action  of  Nitrous  and  Nitric  Acid  and  Diazo-salts  on  Aromatic 
Amines.  Steric  hindrance  also  appears  to  modify  the  action  of 
nitric  and  nitrous  acid  and  diazo  compounds  on  ortho-substituted 
secondary  and  tertiary  bases.  Thus  dimethyl-o-toluidine  and  o- 
methoxy-dimethyl  aniline,  unlike  dimethyl  aniline,  give  no  nitroso 
derivatives,  although  the  para  position  is  free.  Similarly  o-substituted 

1  Ber.,  1905,  38,  1144. 

a  Cohen  and  Dudley,  Trans.  Chun.  Soc.,  1910,  97,  1739. 

8  J.prakt.  Chem.,  1896,  54,  2G5. 


318  ABNORMAL  REACTIONS 

dialkyl  or  acetalkyl  anilines  give  meta-  and  not  para-nitro  deriva- 
tives. Diazobenzene  chloride,  which  readily  forms  an  aminoazo  com- 
pound with  dimethyl  aniline,  reacts  with  difficulty  when  an  ortho- 
substituted  dialkyl  aniline  is  present.  In  these  cases  the  ortho 
substituent  is  supposed  to  influence  the  initial  formation  of  an 
additive  compound  which  is  assumed  to  occur  between  the  nitrogen 
of  the  tertiary  base  and  the  reagent  previous  to  substitution  in  the 
nucleus. 

Reactions  of  Phenylhydroxylamine.  Bamberger  showed  that 
phenylhydroxylamine  unites  with  nitrosobenzene  to  form  azoxy 
compounds,1  and  with  diazobenzene  chloride  to  form  hydroxy  diazo- 
amino  benzene. 

C6H5NHOH  +  NOCCH5        =  C6H5NO=NC6H5  +  H20 
C6H5NHOH  +  C6H5NC1  i  N  =  C6H5N(OH) .  N  :  N  .  CGH5  +  HC1 

The  two  reactions  were  examined  in  the  case  of  a  number  of 
substituted  phenylhydroxylamines  containing  methyl  groups  in  the 
nucleus.  It  was  found  that  where  the  methyl  groups  occupied  the 
ortho  position  to  the  hydroxylamine  group  either  the  speed  of 
the  reaction  or  the  amount  of  the  product  was  greatly  reduced.2 
To  give  one  example,  when  the  unsubstituted  phenylhydroxylamine 
reacts  with  diazobenzene  chloride  a  99  per  cent,  yield  of  the  product 
is  obtained;  the  same  reaction  with  mesitylhydroxylamine  gives 
a  4  per  cent,  yield. 

Action  of  Benzaldehydes  on  Aromatic  Amines.  The  same 
explanation  may  serve  to  explain  the  non-formation  of  triphenyl- 
methane  derivatives  when  union  between  aldehydes  and  o-substituted 
tertiary  bases  is  attempted.  The  reaction,  which  occurs  according 
to  the  following  scheme, 

V  >N(CH3)2 

+  H20 


is  effected  by  attachment  of  the  aldehyde  carbon  to  the  para-carbon 
atom  of  the  amine,  and  there  is  no  obvious  reason  wh}r  ortho  substi- 
tution should  produce  steric  hindrance  unless  some  kind  of  additive 
compound  with  the  tertiary  nitrogen  is  assumed. 

1  For  the  structure  of  azoxy  compounds  see  Angeli,   Gazz.  chim.,  1916,  46, 
ii,  67  ;  and  Ahrens,  Vortrage,  1913. 

a  Bamberger  and  Rising,  Annalen,  1901,  316,  257. 


ACTION  OF  BENZALDEHYDES  ON  AROMATIC  AMINES   349 

If,  in  place  of  a  tertiary  amine,  a  primary  aromatic  amine  is  sub- 
stituted, it  is  the  w-substitution  which  hinders  the  reaction.  Whilst 
o-toluidine  reacts  readily  with  p-nitrobenzaldehyde,  the  wi-compound 
does  so  with  difficulty.  We  must  suppose  here  that  the  aldehyde 
carbon  attaches  itself  directly  to  the  para-carbon  of  the  nucleus. 
That  the  reactions  with  primary  and  tertiaiy  ba"ses  should  afford  so 
curious  a  contrast  in  behaviour  is  somewhat  striking. 

Action  of  Aldehydes  on  Pyridine  Bases.  It  is  well  known 
that  aldehydes  combine  with  a-  and  y-alkyl  pyridine  and  quinoline 
bases.  Konigs1  found  that,  if  formaldehyde  is  used,  the  three 
hydrogen  atoms  of  the  methyl  group  may  all  be  replaced  by 
carbinol  groups  thus : 

/\  /\ 

JCH3     "*     lx/b(CH2OH)3 
N  N 

This  occurs  only  if  the  ortho  position  to  the  methyl  radical  is 
unsubstituted,  otherwise  only  two  carbinol  groups  replace  the 
hydrogen  and  this  applies  to  a-  and  y-methyl  quinolines.  In  the 
latter  case  the  benzene  nucleus  may  play  the  part  of  an  ortho 
substituent  and  resembles  in  this  respect  the  effect  of  the  nucleus 
on  the  esterification  of  a-naphthoic  acid. 

Formation  of  Rosauilines.  The  difficulty  of  combining  aldehydes 
with  meta  substituted  basesjreappears  in  the  formation  of  the  rosani- 
lines,  in  which  p-toluidine  is  oxidised  in  presence  of  primary  aromatic 
amines,  a  reaction  which  in  reality  resolves  itself  into  a  combination 
of  aldehyde  and  amine,  thus : 

NH2 .  C6H4CH3  +  O,  =  NH2 .  C6H4 .  CHO  +  H2O 
NH2 .  C6H4 .  CHO  +  2C6H5NH2  +  O 


NH 


In  the  example  given,  both  ^?-toluidine  and  aniline  may  be  replaced 
by  other  amines  ;  but  Noelting  has  shown  that  if,  in  place  of  aniline, 
meta-amines  like  m-toluidine  and  symm-w-xylidine  are  substituted, 
the  reaction  does  not  take  place.  The  reason  from  the  stereochemical 

»  Bar.,  1899,  32,  223,  3599  ;  1898,  31,  2364. 


350  ABNORMAL  REACTIONS 

standpoint  is  clear  enough,  when  we  consider  that  the  methyl  group 
in  the  meta  position  to  the  carbon  stands  in  the  ortho  position  to  the 
para-carbon  with  which  the  aldehyde  group  always  interacts.  The 
argument  might  be  advanced  that  rosaniline  derivatives,  having 
meta-substituted  groups  are  incapable  of  existence,  but  this  is  met 
by  the  fact  that  indirect  methods  have  been  successfully  used  in 
their  preparation. 

Many  other  examples  of  steric  hindrance  might  be  given,  but  we 
shall  limit  ourselves  to  two  more :  the  action  of  phosphorus  penta- 
chloride  on  hydroxy-acids,  and  of  ammonium  sulphide  on  nitro 
compounds. 

Action  of  Phosphorus  Feutachloride  on  Hydroxy-acids. 
Anschiitz1  and  his  pupils  have  shown  that  the  ordinary  course  of 
the  reaction  between  phosphorus  pentachloride  and  hydroxy-acids 
is  usually  presented  by  the  following  two  equations : 

/OH  /OH 

CCH4<  +  PC15  =  CKH/          +  POC13  +  HC1 

\COOH  \COC1 

/OH  /O.POC12 

CGH4<  +  POC13  =  C6H4<  +  HC1 

\COC1  .  \COC1 

If,  however,  the  two  ortho  positions  to  the  hydroxyl  are  occupied  as 
in  o-methylsalicylic  acid,  the  phosphorus  oxychloride  produces  no 
change  in  the  hydroxyl  group. 

CH3  CH 


OH  +  PC15  =  /        NoH  +  POC13  +  HC1 


COOH  COC1 

Reduction  of  Nitro  Compounds.  The  writer,  in  conjunction 
with  D.  McCandlish,  studied  the  action  of  ammonium  sulphide  on 
a  variety  of  substituted  nitro  derivatives  of  benzene.2  It  was  in- 
variably found  that,  although  the  presence  of  acidic  groups  facilitates 
reduction,  the  nitro  group  was  more  slowly  attacked  by  the  reducing 
agent  if  it  occurred  in  the  ortho  position  to  a  methyl  or  ester  group, 
than  when  present  in  the  meta  or  para  position. 

Chain  Formation.  The  subject  of  steric  hindrance  would 
scarcely  be  complete  without  some  reference  to  the  enormous  mass 
of  detailed  research  which  has  been  accumulated  by  Bischoff  and 
his  collaborators  on  chain  formation  or  conditions  affecting  the 

1  Ber.,  1897,  30,  221.  2  Trans.  Chem.  Soc.,  1905,  87,  1257. 


CHAIN  FORMATION  351 

linking  of  simply  constituted  compounds.  In  carrying  out  these 
researches  he  has  been  guided  by  what  he  terms  the  '  dynamic 
hypothesis '  which  is  merely  an  extension  of  the  principle  of  steric 
hindrance,  and  may  be  explained  as  follows  :  as  the  atoms  or  groups 
in  a  molecule  are  assumed  to  be  in  a  state  of  vibration  or  oscillation, 
a  reaction  will  be  determined  by  the  amount  of  free  space  accorded 
to  the  constituent  groups  undergoing  reaction  or  forming  part  of 
the  new  molecule.  The  interaction  will  then  be  determined  not 
only  by  the  groups  adjoining  the  reacting  constituent  in  each  of  the 
molecules,  as  suggested  by  V.  Meyer,  but  also  by  the  disposition  of 
the  groups  in  the  resulting  product.  This  second  condition  plays 
an  important  role,  according  to  Bischoff ;  for  he  supposes  the  atoms 
in  a  chain  to  assume  a  curved  arrangement  (p.  179)  so  that  in  a  chain 
of  5  or  6  atoms  the  first  and  last  will  be  in  closer  proximity  than 
the  first  and  third  or  the  first  and  fourth  of  the  chain. 


The  groups  attached  to  the  fifth  and  sixth  atoms  of  the  chain, 
which  are  termed  the  critical  positions,  will  therefore  be  a  deter- 
mining factor  equally  with  those  attached  to  the  reacting  groups. 
As  in  the  *  esterification  law '  the  chemical  nature  of  the  molecules 
is  not  taken  into  account. 

We  cannot  pretend  to  review  the  whole  of  the  materials ;  but  it 
may  be  pointed  out  that  steric  influences,  though  not  always  con- 
sistent with  Bischoff  s  hypothesis,  are  throughout  clearly  in  evidence 
as  factors  determining  chemical  change.  A  few  examples  must 
suffice. 

Sodium  malonic  ester  and  sodium  acetoacetic  ester  react  with 
a-bromo-fatty  esters  as  follows  : 

/COOC2H5  CH(COOC2H5)2 

CHNa<  +  CH2Br .  COOC2H5  =  |  +  NaBr 

\COOC2H5  CH2 .  COOC2H5 

CH3 .  C(ONa) :  CH .  COOC2H5  +  CH2Br .  COOC2H5 

=  CH3 .  CO .  CH .  COOC2H,  +  NaBr     , 

CH2.COOC2H5 


352  ABNORMAL  REACTIONS 

In  the  product  of  the  first  reaction  the  longest  uninterrupted  chain 
of  carbon  atoms  is  four,  in  that  of  the  second  reaction,  five,  or,  in 
other  words,  the  second  reaction  involves  one  of  the  critical  positions, 
which  should  manifest  itself  in  a  diminished  yield.  Again,  by 
introducing  alkyl  groups  into  the  reacting  group  of  the  fatty  acid 
or  into  that  of  malonic  and  acetoacetic  ester,  free  vibration  of  these 
alkyl  groups  would  be  affected  and  a  diminished  yield  should  again 
follow.  The  experimental  evidence  agrees  substantially  with  the 
results  anticipated  by  the  theory.  Malonic  ester  reacts  more  readily 
than  acetoacetic  ester  or  than  its  own  alkyl  or  dialkyl  derivatives, 
and  moreover  it  reacts  more  readily  with  a  normal  than  with  an 
iso-bromo  fatty  acid,  and  finally  the  two  react  more  readily  the 
shorter  the  carbon  chain  in  the  alkyl  groups.  For  example,  if 
sodium  methyl  malonic  ester  and  a-bromo  isobutyric  ester  are  boiled 
together  in  alcoholic  solution,  the  reaction  proceeds  abnormally  in 
the  following  manner,  in  which,  instead  of  the  a-carbon,  *C  becomes 
linked  to  the  malonic  ester  molecule. 

COOR       *CH3  COOR 

I  I  I 

CH3CNa     +  BrC .  COOR  =  CH3 .  C— CH2-  CH .  COOR  +  NaBr 

COOR        CH3  COOR       CH3 

In  xylene  solution,  however,  the  reaction  takes  its  normal  course. 

Similar  experiments  have  been  carried  out  with  a  series  of  sodium 
alcoholates  and  substituted  phenates  on  the  one  hand  and  a-bromo 
fatty  acids  on  the  other  with  much  the  same  general  result. 

R .  ONa  +  BrCH2 .  COOC2H5  =  R .  O .  CH2 .  COOC2H5  +  NaBr 

For  example,  whilst  sodium  o-nitrophenate  and  a-bromopropionic 
ester  combine  in  a  normal  fashion, 

,N02  yN02 

C6H/         +  CH3 .  CHBr .  COOR  =  C,H4<;         /CH3     +  NaBr 
X)Na  \0  •  CH 

\COOR 
no  reaction  occurs  with  a-bromo  isobutyric  ester. 

Another  reaction  of  a  similar  nature  is  the  union  of  substituted 
aromatic  amines  containing  radicals  in  the  nucleus  as  well  as  in  the 
amino  group  with  a-bromo  fatty  acids  according  to  the  equation  : 

C6H5NH2  +  Br .  CH2 .  COOC2H5  =  C6H5NH .  CH2 .  COOC2H5  +  HBr 

In  the  last  three  reactions  Bischoff  includes  the  oxygen  and 
nitrogen  atoms  as  part  of  the  chain. 

In  reviewing  the  foregoing  results  it  must  be  admitted  that  a 


CHAIN   FORMATION  353 

strong  case  has  been  made  out  for  the  principle  of  steric  hindrance. 
At  the  same  time  a  fact,  which  has  been  frequently  emphasized,  must 
not  be  overlooked,  namely,  the  presence  of  certain  groups  which  by 
their  chemical  nature  counteract  certain  expected  changes.  In 
illustration  of  this,  it  has  been  pointed  out  by  Stewart1  that  the 
formation  of  bisulphite  compounds  of  ketones  is  determined  by  the 
nature  of  the  radicals  attached  to  the  ketone  group ;  that  whilst 
the  increase  in  the  size  of  the  hydrocarbon  radical  retards,  the 
presence  of  carboxyi  facilitates  bisulphite  formation. 

Again,  Auwers  and  Perkin  find  that,  whereas  methylacrylic  acid 
condenses  readily  with  sodium  malonic  ester,  dimethylacrylic  acid 
gives  a  very  small  yield,  and  trimethylacrylic  acid  refuses  to  react. 
This  may  be  merely  a  case  of  the  positive  alkyl  groups  aifecting  the 
whole  character  of  the  compound  and  not  necessarily  one  of  interfer- 
ence, just  as  the  additive  power  of  defines  for  bromine  is  diminished 
by  the  attachment  of  negative  groups,  such  as  carboxyi,  ester  and 
phenyl  groups,  or  bromine  atoms  to  the  doubly  linked  carbons.  The 
concurrent  influences  of  position  and  character  of  the  group  are  not 
always  easy  to  differentiate,  but  for  that  very  reason  the  conclusion 
that  an  apparently  anomalous  reaction  is  to  be  placed  to  the  account 
of  steric  influences  should  be  made  with  caution. 

It  must  be  confessed  that  we  are  still  profoundly  ignorant  of  the 
change  which  substituents  effect  in  the  character  of  the  molecule  as 
a  whole,  the  causes  which  determine  the  rules  of  orientation,  the 
reason  why  positive  groups  like  methyl  and  amino  groups  facilitate 
nitration,  sulphonation,  acetylation  by  the  Friedel-Crafts  method,2 
&c.,  why  negative  groups  assist  hydrolysis  of  cyanides,  reduction  of 
nitro  groups,  acetal  formation,  &c.,  and  a  host  of  other  phenomena 
of  a  similar  nature.  Until  clearer  views  obtain  on  these  subjects  it 
can  scarcely  be  hoped  that  real  progress  will  be  made  on  the  nature 
of  chemical  change.  The  expression  '  steric  hindrance '  meantime 
affords  a  useful  if  not  very  appropriate  title  for  docketing  a  number 
of  allied  phenomena. 

REFERENCES 

Der  Einfluss  der  Raumerfiillung  der  Atomgruppen,  by  M.  Scholtz.  Ahrens'  Vortrage, 
1899,  4,  833.  Enke,  Stuttgart. 

Ueber  den  Einfluss  der  Kernsubstitution  auf  die  Reaklionsfahigkeit  aromatiscJier  Verbin- 
dungen,  by  J.  Schmidt.  Ahrens'  Vortrage,  1902,  7,  283.  Enke,  Stuttgart. 

Lehrbuch  der  Stereochemie,  by  A.  Werner.    Fischer,  Jena,  1904. 

Stereochemistry,  by  A.  W.  Stewart.     Longmans.  1907. 

1  Trans.  Cliem.  Soc.,  1905,  87,  185. 

»  V.  Meyer,  Bar.,  1896,  29,  1413,  25G4  ;  Kunckell  and  Hildebrandt,  B*r.t  1901, 
34,  1826. 

PT.  i  A  a 


INDEX  OF  SUBJECTS 


Abnormal  reactions,  330. 
Acceptor,  122. 

Acetals,  15 ;  formation  of,  343. 
Acetic  acid,  2;  esterification  constant, 

341. 

Acetic  ether,  6,  9,  14,  16. 
Acetoacetic  ester,  properties  of,   222; 

synthesis  of,  220 ;  formation  of,  228. 
Acetosuccinic  ester,  191. 
Acety  1  radical,  15. 
Acety  lace  tone,  233. 
Acety  Icy  clop  ropane    carboxylic    acid, 

194. 

Acetylchloranilide,  278. 
Acetylene    compounds,   reduction  of, 

165  ;  structure  of,  73. 
Acetylidene  compounds,  73. 
Acids,  affinity  constants  of,  336,  341 ; 

esterification  of,  341,  366 ;  molecular 

weight    of,    8;     reduction   of,    167; 

structure  of,   7;    synthesis  of,   188, 

196,  213. 

Aconitic  acid,  structure  of,  82. 
Acyl    chlorides,    action   on    alcohols, 

346 ;  hydrolysis  of,  344. 
Addition,  111;    of  bromine,  116;    hy- 
drogen, 116 ;  hydrogen  cyanide,  205  ; 

hydroxyl,  119;    nitrogen  tetroxide. 

119  ;  nitrogen  trioxide,  119 ;  nitrosyl 

chloride,  119;  ozone,  119. 
Addition  products  of,  aldehydes,  128 ; 

carbon     suboxide,    129 ;      ethenoid 

compounds,    113;       ketenes,     129; 

ketones,    128;     thialdehydes,    128; 

thioketones,  128. 
Additive  reactions,  111,  201. 
Adipic  acid,  188. 
Affinity  and  valency,  107. 
Affinity  constants    of   organic    acids, 

336,341. 

Affinity,  primary  and  secondary,  104. 
Alcarsin,  13. 
Alcohol,  constitution  of,  2,  6,  9,  10,  14, 

16,  41. 
Alcohols,  synthesis  of,  188,  196,  207, 

210;    oxidation  of,   321;    action  of 

acid  chlorides,  346.    *"*" 
Aldehydes,    formation    of,    196,    212; 

reduction  of,  166. 
Aldol  condensation,  174,  237. 
Aldoxinies,  synthesis  of,  189,  196. 
Aliphatic    amines,    168 ;     diazoamino 

compounds,  215. 

PT.  I.  A 


Alkylainmonium  cyanate,  transforma- 
tion of,  313. 

Alkylammonium  iodides,  formation  of, 
346. 

Alkylation  of  bases,  347 ;  of  phenols, 
347. 

Alkylglutaconic  acids,  isomerism  of, 
78. 

Alkyliodides,  action  of  silver  salts,  303. 

Aluminium  chloride,  as  condensing 
agent,  195. 

Aluminium-mercury  couple,  198,  199. 

Amide  radical,  16. 

Amides,  hydrolysis  of,  331,  344 ;  syn- 
thesis of,  214. 

Amines,  synthesis  of,  170. 

Amino-azobenzene,  colour  of,  148. 

Ammonium  cyanate,  transformation 
of,  295. 

Amyl  alcohol,  15. 

Anhydrides,  reduction  of,  167. 

Anthracene,  hydrides,  166,  170;  poly- 
merisation of,  324. 

Aromatic  acids,  hydrides,  169 ;  syn- 
thesis of,  196. 

—  aldehydes,  synthesis  of,  196. 

—  aldoximes,  synthesis  of,  196. 

—  bases,  action  of  nitrous  and  nitric 
acids,  347 ;    of  diazo  salts,  347 ;    of 
benzaldehyde,   348;     reduction    of, 
168. 

—  compounds,  15. 

Aromatic  hydrocarbons,  formation  of, 
195 ;  reduction  of,  167 ;  synthesis 
of,  188. 

—  ketones,  synthesis  of,  195. 

—  series,  substitution  in,  149. 
Atomic  number,  58,  97. 

—  refractivity,  85. 

—  volume,  85. 

—  weights,  of  Berzelius,  3 ;  of  Dumas, 
5  ;  of  Gerhardt,  27. 

Atoms,  molecules  and  equivalents  of 
Laurent,  30. 

Autoxidation,  121. 

Autoxidator,  122. 

Auxiliary  valency,  90. 

Azimidobenzene,  265. 

Azo  colouring  matters,  reaction  velo- 
city, 294. 

Barred  atoms,  6,  48. 
Base,  2. 


856 


INDEX  OF  SUBJECTS 


Basic  water,  7. 

Basicity  of  acids,  23,  28. 

Beckmann's  reaction,  255. 

Beer's  law,  64. 

Benzalacetone,  147. 

Benzalaniline,  formation  of,  333. 

Benzaldehyde,  abnormal  reactions  of, 

348,  349. 
Benzene,   15 ;     from   acetylene,    201  ; 

chlorination  of,  302. 
Benzoic  acid,  1,  7;  radical  of,  1,  11. 
Benzoin  condensation,  245. 
Benzoyl  acetone,  233. 
Benzoylacetophenone,  233. 
Benzoylbenzoic  acid,  197. 
Benzoyl  hydroperoxide,  123. 
Benzpinacone,  246. 
Benzylidene  acetone,  239. 
Benzylsulphinic  acid,  198. 
Binary  compounds,  8. 
Bisulphite  compounds  of  ketones,  128. 
Bivalent  carbon,  65. 
Bromination,  dynamics  of,  327. 
Bromindoxyl,  187. 
Bromine,  addition  of,  116. 
Bromotriphenylmethyl  chloride,  62. 
Buchner-Curtius  reaction,  204. 
Butyrobutyric  ester,  225. 

Cacodyl,  12. 

Cadet's  fuming  liquid,  12. 

Camphoric  acid,  esterification  of,  342. 

Camphoronic  acid,  synthesis,  219. 

Carbamide,  decomposition,  316. 

Carbithionic  acid,  214. 

Carbon,  bivalent,  65 ;    inertia  of,  108  ; 

plasticity  of,   108;     tervalent,    59; 

valency  of,  56. 

—  bonds,  equivalents  of,  83. 

—  suboxide,  129. 

—  -nitrogen,   chain    formation,   254; 
ring  formation,  257,  258;  stability 
of,  255 ;    substitution  methods,  254 ; 
additive  methods,  255. 

oxygen,  chain  formation,  268 ;  ring 

formation,  268. 

Carbonyl  compounds,  action  of  halo- 
gens, 318. 

Carbopyrotritaric  acid,  270. 

Carbyloxime,  71. 

Catalysed  reactions,  dynamics  of,  326. 

Catalysis,  applied  to  ether  formation, 
44. 

Catalysts,  metals,  154 ;  metallic  oxides, 
169. 

Catalytic  reactions,  162 ;  condensation, 
173;  halogenation,  172;  oxidation, 
171 ;  reduction,  162. 

Chain  formation,  174  ;  carbon-carbon, 
174  ;  carbon-nitrogen,  254  ;  carbon- 
oxygen,  268 ;  eftect  of  sterie  hin- 
drance, 350, 

Chelidonic  acid,  272. 


Chemical  types,  21. 

Chloral,  6,  15,  16. 

Chlorination  of  benzene,  velocity  of. 
302. 

Chloroacetanilide,  278. 

Chloroform,  6,  15. 

Chloronaphthonitrile,  hydrolysis  of, 
330. 

Chloronaphthoic  acid,  esterification 
of,  337. 

Chloroquinoneoximes,  formation  of, 
332. 

Chrysin,  274. 

Cinnamic  acid,  synthesis  of,  249. 

Cinnamic  aldehyde,  239. 

Cinnamyl  radical,  12. 

Citric  acid,  synthesis  of,  218. 

Claisen  reactions,  235,  238. 

Colloidal  metals,  162. 

Comanic  acid,  272. 

Comenic  acid,  272. 

Composite  reactions,  298. 

Compound  radical,  11,  13,  16. 

Concurrent  reactions,  299. 

Condensation  processes,  174  ;  catalytic 
173;  by  addition,  201 ;  external,  175; 
internal,  175;  nature  of,  176;  by 
removal  of  carbon  dioxide,  200 ;  by 
removal  of  halogens,  188;  by  re- 
moval of  hydrogen,  187;  by  removal 
of  hydrogen  chloride,  194  ;  with  ring 
formation,  175  ;  by  union  of  carbon- 
carbon,  174. 

Condensation  processes,  acetoacetic 
ester,  220 ;  aldol,  237  ;  benzoin,  245  ; 
pinacone,  246 ;  magnesium  alkyl, 
208 ;  zinc  alkyl,  206. 

Condensed  types,  47. 

Conjugated  compounds,  26,  32. 

Conjugated  double  bonds,  132. 

Conjunct,  32,  36. 

Consecutive  reactions,  314. 

Constitution  of  organic  acids,  22,  35; 
of  organic  compounds,  36,  39. 

Contravalency,  58. 

Co-ordinate  number,  92. 

Copper,  condensing  agent,  199. 

Copula,  32,  36. 

Copulated  compounds,  87. 

Coumalinic  acid,  272. 

Coumarin,  248. 

Crossed  double  bonds,  137. 

Cyanacetic  acid,  properties  of,  190, 
192  ;  affinity  constant,  71. 

Cyanainide,  polymerisation  of,  174. 

Cyanides,  structure  of,  67. 

Cyannic  acid,  polymerisation  of,  174. 

Cyanogen  radical,  12. 

Cyanogen  chloride,  polymerisation  of, 
174. 

Cyclic  compounds,  action  of  reagents, 
181  ;  evidence  of,  182  ;  formation  of, 
178,  192,  200,  203 ;  stability  of,  181 ; 


INDEX  OF  SUBJECTS 


.    synthesis  of,  192;    transformations 

of,  183. 

Cyclic  ketones,  synthesis  of,  200. 
Cyclobutane,  182,  185,  193. 
Cyclobutanol,  184. 
Cyclobutene,  185. 
Cyclobutylamine,  184. 
Cyclobutylnaethylamine,  184. 
Cycloheptane,  186,  247. 
Cyclohexadiono,  185. 
Cyclohexane,  1C6,  169,  170,  185,  189; 

derivatives  of,  191,  194,  197. 
Cyclohexane  carboxylic  acid,  226,  227. 
Cyclohexanol,  166,  167. 
Cyclohexanone,  166. 
Cyclohexylamine,  170. 
Cyclohexylmethylamine,  184. 
Cyclo-nonane,  186. 
Cyclo-octadiene,  186. 
Cyclo- octane,  186. 
Cyclo-paraffins,    action     of    reagents, 

"l80;      heat    of    combustion,     182; 

properties  of,  187  ;  .synthesis  of,  185, 

189,  200. 
Cyclopentane,  185,  200;  derivatives  of, 

193,  200. 

Cyclopentauol,  184. 
Cyclopentanone,  250,  253. 
Cyclopentene,  derivatives  of,  184,  238. 
Cyclopropane,  182,  185,  189. 
—  carboxylic  acids,  180,  193,  204. 
Cyclopropyl  carbinol,  184. 

Dehydracetic  acid,  273. 

Dehydration,  170. 
Dehydrogenation,  169. 

Diacetosuccinic  ester,  191. 
Dialkylmalonic  esters,  action  of  am- 
monia, 344. 

Diazoamino-compounds,  conversion. 
286 ;  synthesis,  215. 

Diazo-compounds,  action  on  aromatic 
amines,  347;  on  phenylhydroxyl- 
amine,  348 ;  velocity  of  decomposi- 
tion. 293. 

Diazoles,  258. 

Diazomethane,  synthetic  use,  204. 

Dibasic  acids,  synthesis,  188;  elec- 
trolysis, 200. 

Dibenzalacetone,  239. 

Dibenzylidene  acetone,  239. 

Dicyclohexylamine,  168. 

Dihydrocamphene.  166. 

Dihydrocavveol,  167. 

Dihydroresorcinol.  226. 

Dihydroxyterephthalic  ester,  225. 

Diisobutylene,  187. 

Diketoapocamphoric  acid,  227. 

Diketocyclopentane  dicarboxylic  acid, 
227. 

Diketones,  190,  200. 

Dimethylacrylie  acid,  condensation  of, 
853. 


Dimethylmesidine,  330. 
Dimethylsuccinic  acid,  192;  esttrifica- 

tion  of,  342. 
Dimethylxylidines,     methylation     of, 

330. 

Di-ortho  acids,  334,  340. 
Diphenyl  ether,  200. 
Diphenylmethane,  243. 
Diphenylnitride,  65. 
Diphenylpropionic  acid,  201. 
Dissociation  constants  of  organic  acids, 

341. 

Ditolyl,  199. 
Double  bond,  conjugated,  132 ;  crossed, 

137  ;  theory  of,  74. 
Duroquinone,  241. 
Durylic  acid,  334. 
Dynamics  of  organic  reactions,  275. 

Electrochemical   theories  of  valency, 

96. 

Electrolysis  of  acids,  200. 
Electronic  theory  of  substitution.  160  ; 

of  valency,  97,  98. 
Electrons,  97. 
Enzyme  hydrolysis,  289. 
Equivalence  of  carbon  bonds,  83. 
Esterification  in  alcohol  solution,  290 

dynamics  of,  312. 

—  constants,  335,  341. 

—  law,  334. 

Esters,  hydrolysis  of,  2S7,  343;  syn- 
thesis of,  213. 

Ethane  tetracarboxylic  acid,  191. 

Ethenoid  compounds,  113. 

Ethylene  bond,  132;  crossed,  137 
stereochemistry  of,  75 ;  theory  of,  74 

External  condensation,  175. 

Faraday's  law,  57. 

Fatty  acids,  esterification  of,  041. 

Fenton's  reagent,  172. 

Ferric  chloride,  condensing  agent,  195 

Formaldehyde,  condensation  of,  243. 

Formylhippuric  acid,  234. 

Formylphenylacetic  ester,  227. 

Free  valencies,  77. 

Friedel  Krafts  reaction,  195  ;    velocifr 

of,  297. 

Fulminic  acid,  structure  of,  71. 
Furfuraldehyde,  269. 
Furfurane,  268. 
Furfurole,  269. 

Glutaconic  acids,  78. 
Glycerol,  2,  8. 
Glyoxalines,  262. 
Grignard's  reaction,  208. 

Halogenation,  catalytic,  172. 

Halogen  carriers,  173. 

Halogen  compounds,  reduction  of.  161 


858 


INDEX  OF  SUBJECTS 


Halogens,  action  on  cthenoid  com- 
pounds, 318,  310. 

Heat  of  combustion,  of  defines,  75;  of 
paraffins,  75. 

Hemimellitic  acid,  esterification  of, 
335. 

Hemipinic  acid,  esterification  of,  339. 

Heterogeneous  addition,  124. 

Hexamethyl benzene,  202. 

Hexaphenylethane,  65. 

Historical  introduction,  1 ;  references, 
55. 

Homocamphoric  acid,  esterification  of,^ 
342. 

Homologous  compounds,  30. 

Homoplithalic  nitrile,  hydrolysis  of, 
331. 

Hydrindone,  197. 

Hydrobenzoin,  246. 

Hydrocarbons,  synthesis  of,  195,  210. 

Hydrochloric  ether,  9,  14. 

Hydrogen,  addition  of,  116. 

Hydrogen  cyanide,  addition  of,  K>r, ; 
structure  of,  69. 

Hydrolysis  of  acyl  chlorides,  344  ;  of 
amides,  344;  of  cyanides,  345;  of 
esters,  279,  287,  343;  of sucrosp,  287  ; 
by  enzymes,  289. 

Hydroxyacids,  195;  action  of  phos- 
phorus chlorides,  350. 

Hydroxyaldehydt-8,  195. 

Hydroxyanthraquinone,  172. 

Hydroxybenzylalcohol,  243. 

Hydroxyl,  addition  of,  119. 

Hydroxylamine  compounds,  synthesis 
of,  215. 

Ilydroxymethylene  camphor,  235. 

—  compounds,  235. 

Hydroxynaphthoic  acid,  esterification 
of,  337. 


Iminazoles,  2C2. 

Iminoethers,  formation  of,  331. 

Indole,  168. 

Indoxyl,  187. 

Internal  condensation,  175. 

Intramolecular  ionization,  99. 

—  isomeric  change,  177;   velocity  of, 

278. 

Ionic  molecules,  99. 
lonone,  239. 
Irone,  240. 
Isacetophorone,  244.. 
Isobutylene,  187. 

Isocamphoronic  acid,  synthesis  of,  203. 
Isocyanides,  additive  compounds.  66 ; 

structure  of,  66. 
Isomeric  change,  intramolecular,  177; 

velocity  of,  278. 
Isomerism,  9. 

Isophenylcrotonic  acid,  249. 
Isopulegol,  240. 


Ketimines,  132. 

Keto-enol  tautomerism,  reaction  velo- 
city, 320. 

Ketones,  addition  products,  128 ; 
action  of  halogens,  318 ;  reduction 
of,  166;  synthesis  of,  195,  207,  213. 

Ketonic  acids,  201;  synthesis  of,  216. 

Lactones,  formation  of,  311. 

Law  of  Dulong  and  Petit,  3 ;  of  even 

numbers,  28;   of  mass  action,  275; 

of  substitution,  17. 

Malic  acid,  2. 

Malonic  ester,  properties  of,  191. 

Mass  action,  law  of,  275. 

Mechanical  types,  21. 

Meconic  acid,  272. 

Melamine,  174. 

Mellitic  acid,  hydrolysis  of,  839. 

Menthane,  166. 

Mercaptans,  15,  16. 

Mercury  fulminate,  71. 

Mesitylacetic  acid,  335. 

Mesityl  aldehyde,  333. 

Mesitylene  carboxylic  acid.  836, 

Mesitylene  from  methylacetylene,  202. 

Mesitylglyoxylic  acid,  333,  33oi 

Mesityl  oxide,  238. 

Mesityloxide  oxalic  ester,  227. 

Metalammine  compounds,  92,  94,  102. 

Metallic  cyanides,  67. 

Metals,  colloidal,  162;  used  in  reduc- 
tion, 164. 

Method  of,  see  Reaction  of. 

Methylcyclobutane,  185,  189. 

Methylcyclohexane,  184. 

Methylcyclopentane,  184. 

Methyldehydropentone  carboxylic 
ester,  194. 

Methyl  furfurane,  167. 

Methyl  granatinine,  186. 

Mixed  types,  48. 

Modern  structural  formulae,  202. 

Molecular  compounds,  93. 

Molecular  types,  21. 

Molecular  weights,  of  Berzelius,  3 ;  of 
Dumas,  5;  of  organic  acids,  8;  of 
Gerhardt  and  Laurent,  30. 

Moloxide,  122. 

Morphium,  8. 

Mutarotation,  dynamics  of,  310;  of 
monosaccharoses,  310. 

Naphthalene-diamine,  253. 
Naphthalene  hydrides,  166. 
Naphthenes,  166. 
Naphthol  hydrides,  166. 
Negative-positive  rule,  114. 
Neutral  affinities,  99. 
New  theory  of  types,  44. 
Nitriles,  hydrolysis  of,  331. 


INDEX  OF  SUBJECTS 


Nitrocamphor,  dynamic  isomerism,  308. 
Nitro-compounds,   167;    reduction  of, 

350. 
Nitrogen  tetroxide,  addition  of,  119. 

—  trioxide,  addition  of,  119. 
Nitrophthalic   acids,  esterification  of, 

338. 

Nitrosyl  chloride,  addition  of,  119. 
Non-polar  compounds,  104. 
Non-reversible     reactions,     polymole- 

cular,  279  ;    termolecular,  281 ;   uni- 

molecular,  277. 
Normal  valency,  58. 
Nucleus  theory  of  Laurent,  18. 

Octylaldol,  238. 

Oil  of  Dutch  chemists,  9. 

—  of  wine,  9. 
Olefiant  gas,  9,  16. 

Olefines,  116;  reduction  of,  165. 
Order  of  a  reaction,  determination  of, 

282;   initial  velocity   method,  283; 

isolation   method,   285 ;   method  of 

equifractional   parts.  284  ;   velocity 

coefficient  method,  286. 
Organic  acids,  constitution  of,  23. 

—  analysis,  8. 

Organic  chemistry  in  1830,8;    1830- 
1840,  15. 

—  synthesis,  9. 

—  reactions,  dynamics  of,  275  ;  nature 
of,  107. 

Organo-metalliccompounds,  35, 37, 205. 
Origin  of  the  radical  theory,  1. 
Oxalacetic       acid      phenylhydrazone, 

velocity  of  decomposition,  300. 
Oxalacetic  ester,  218,  227. 
Oxalic  acid,  2,  7. 
Oxalic  ester,  6,  9. 
Oxamethane,  10,  16. 
Oxidation,   action    on    alcohols,    321  ; 

catalytic,  171. 
Ozone,  addition  of,  119. 
Ozonides,  120. 
Ozotriazoles,  263. 

Paraffins,  36  ;  heat  of  combustion,  75; 

synthesis  of,  188,  205. 
Partial  valencies,  133. 
Pentabromobenonitrile,  hydrolysis  of, 

330. 
Pentachlorobenzonitrile,  hydrolysis  of, 

330. 
Pentamethylaminobenzene,   methyla- 

tion  of,  330. 
Pentamethylbenzamide,  hydrolysis  of, 

330. 

Pentamethylbenzoic    acid,    esterifica- 
tion of,  336. 
Pentamethylbenzonitrile,     hydrolysis 

of,  330. 
Petroleum,  American,  165  ;  Caucasian, 

165- ;  Galician,  165. 


Phenantbrene  hydrides,  164. 
Phenols,  production  of,  166. 
Phenylamino-benzoic  acid,  199. 
Phenylangelic  acid,  251. 
Phenylcrotonic  acid,  250. 
Phenylcyclohexylamine,  168. 
Phenyldihydroxyresoreyclic  ester,  203, 
Phenylglycinecarboxylic  ester,  199. 
Phenylhydroxypivalic  acid,  250. 
Phenylparaconic  lactones,  250. 
Phloroglucinol  tricarboxylic  ester.  226, 
Phorone,  238. 
Phosphorus  chloride,    action   on    hy- 

droxyacids,  350. 
Photochemical  reactions,  322. 
Pinacone  condensation,  246. 
Pinane,  166. 

Piperidine,  170,  255,  346. 
Platinum  compounds  of  Zeise,  10. 
Polar  compounds,  104. 
Polybasic  acids,  theory  of,  23. 
Polymerisation,  173;   action  of  light, 

174. 
Polymolecularnon-reversiblereactions, 

279. 

Positive  negative  rule,  114,  191. 
Primary  affinity,  104. 
Primary  alcohols,  synthesis  of,  207.  210, 
Primary  nuclei,  18. 
Principal  valency,  90. 
Propiopropionic  acid,  224. 
Pserfdoionone,  239. 
Pseudopelletierine,  186. 
Puligomenthol,  166. 
Pyrazole,  255. 

Pyrazole  compounds,  204,  255. 
Pyrazolidone  compounds,  261. 
Pyrazolone  compounds,  261. 
Pyridine  bases,  action   of  aldehydes, 

349. 

Pyromeconic  acid,  272. 
Pyromellitic  acid,  esterification  of,  338. 
Pyromucic  acid,  270. 
Pyrone  compounds,  271. 
Pyrotritaric  acid,  270. 
Pyrrole  compounds.  259. 
Pyrrolidine,  257,  259. 
Pyrrolidone,  259. 
Pyrroline,  259. 

Quadrimolecular  reactions,  281. 
Quinitol,  169. 
Quinocarbonium  salt,  63. 
Quinol,  62. 

Quinoline,  steric  hindrance,  349. 
—  tetrahydride,  168. 
Quinone  di-imine,  140. 
Quinone  imine,  146. 
Quinonoximes,  formation  of,  332. 

Radical,  of  benzoic  acid,  1 ;  simple 
and  compound,  3 ;  attempts  to 
isolate,  34;  polyatomic,  49. 


360 


INDEX  OF  SUBJECTS 


Radical  theory,  origin  of,  1 ;  growth 

of,  11. 
Reaction    of    Buehner-Curtius,    204 ; 

Claisen,  235,  238  ;  Crum-Brown  and 

Walker,     200;       Frankland,     206; 

Freund,    189;    Friedel-Crafts,    195, 

297  ;  Grignard,  208  ;  Hofmann,  185  ; 
Ipatiew,  168;  Kekule,  188;  Knoeve- 
nagel,   241;    Michael,  202;    Perkin, 
192,    248;     Perkin,    jr.,    189,    192; 
Reformatsky,     217 ;       Reimer  -  Tie  - 
mann,  195;  Sabatier-Senderens,  164; 
Thorpe,  252;    Ullmann,  199;    Wis- 
licenus,    188,    189;     Walker,    200; 
Wurtz,  188. 

Reactions,  additive,  111,  201 ;  action  of 
solvent,  326 ;  bimolecular,  279 ;  cata- 
lysed, 326 ;  catalytic,  162 ;  composite, 

298  ;    concurrent,  299  ;    consecutive, 
314 ;     heterogeneous,    328 ;    non-re- 
versible, 277  ;   order  of,  282 ;   photo- 
chemical, 322 ;  polymolecular  non- 
reversible,  279 ;  reversible,  306 ;  tor- 
molecular  non-reversible,  281  ;  types 
of,  109;  unimolecular  non-reversible, 
277  ;  velocity  of,  277. 

—  of  unsaturated    compounds,    111, 
201 ;  of  ketones,  128. 

—  abnormal,  330. 
Reagent  of  Fenton,  172. 
Reagents,  action  of,  180. 
Reduction,  catalytic,  162. 

—  of  acetylene,  165  ;   acids,  167  ;  alde- 
hydes, 166;    anhydrides,  167;    aro- 
matic bases,  168. 

—  aromatic  hydrocarbons,   166 ;     cy- 
anides,   167 ;    halogen    compounds, 
168 ;  isocyanides,  167  ;  ketones,  166  ; 
nitro-compounds,  167  ;  olefines,  165  ; 
oximes,    167 ;     phenols,   166 ;     un- 
saturated acids,  esters  and  ketones, 
167. 

Residues,  theory  of,  26. 

Reversible  reactions,  305. 

Ring  structures,  action  of  reagents, 
180  ;  carbon-nitrogen,  257  ;  carbon- 
oxygen,  268;  evidence  of,  182; 
formation  of,  178 ;  stability  of,  179 ; 
transformation  of,  183. 

Rosanilines,  formation  of,  349. 

Rule  of  Crum-Brown  and  Gibson,  149 ; 
of  Markownikoff,  114;  of  Michael, 
114;  of  Vorlander,  150. 

Sabinaketone,  214. 
Sabinene,  220. 
Salicyl  radical,  12. 

Secondary  alcohols,  synthesis  of,  206, 
210. 

—  bases,  acetylation  of,  347. 
Sels  copules,  27. 

Sodamide,  as  condensing  agent,  233. 
Steric  hindrance,  330 ;  in  ester  forma- 


tion, 334,  340;  in  hydrolysis  of 
amides,  331,  344  ;  of  acyl  chlorides, 
344;  of  cyanides,  331,  345;  the 
union  of  acyl  chkmdes  and  alcohols, 
346 ;  formation  of  alkylammonium. 
iodides,  346 ;  acetylation  of  secondary 
bases,  347 ;  action  of  nitrous  and 
nitric  acid  and  diazonium  salts  on 
aromatic  amines,  347;  action  of 
aldehydes  on  pyridine  bases,  349 ; 
alkylation  of  bases  and  phenols,  347  ; 
action  of  benzaldehyde  on  aromatic 
amines,  333,  348 ;  action  of  phos- 
phorus chloride  on  hydroxy-acids, 
350  ;  formation  of  rosanilines,  349 ; 
action  of  phenylhydroxylamine  on 
nitrosobenzene,  and  diazonium 
salts,  348;  hydrolysis  of  esters,  843; 
reduction  of  nitro-compounds,  350; 
chain  formation,  350. 

Steric  hindrance,  theory  of,  342,  351  ; 
theory  of  Victor  Meyer,  334;  of 
Wegscheider,  342;  of  Bischoff, 
350. 

Strain  theory,  76,  178. 

Structure  of  acetylene  compounds,  73  ; 
aconitic  acid,  82;  cyanides,  67;  ful- 
minic  acid,  71 ;  hydrogen  cyanide, 
69;  isocyanides,  66;  triphenyl- 
methyl,  60. 

Substituted  acetic  acids,  esterification 
of,  341. 

Substitution,  electronic  theory,  160 ; 
in  aromatic  compounds,  149;  in 
benzene,  150;  theories  of,  17,  152; 
velocity  of,  305. 

Succinosuccinic  ester,  225. 

Sucrose,  hydrolysis  of,  287. 

Sulphovinic  acid,  9,  11,  14. 

Sulphur  acids,  synthesis  of,  214. 

Synthesis,  acetoacetic  ester,  220 ;  acids, 
195  ;  acyl  chlorides,  197  ;  alcohols, 
188,  196,  207,  210;  aldehydes,  196, 
212;  amides,  212  ;  aromatic  hydro- 
carbons, 188,  189  ;  cyclic  compounds, 
185,  192  ;  cyclo-paraffins,  185 ;  diazo- 
amino-compounds,  215  ;  esters,  213, 
217;  hydrocarbons,  189,  195,  210; 
hydroxylamine  derivatives,  196,  215  ; 
ketones,  195.  208,  213. 


Termolecular  non-reversible  reactions, 

281. 
Tertiary  alcohols,    synthesis   of,    206, 

210. 

Tervalent  carbon,  59. 
Tetramethylbenzonitrile,      hydrolysis 

of,  330. 

Tetraphenylethane,  65. 
Tetraphenyloctazene,  257» 
Tetrazoles,  259,  266. 
Tetronic  acid,  271. 


INDEX  OF  SUBJECTS 


361 


Theory,  electrochemical,  96;  electronic, 
97. 

—  of  benzene  substitution,  150  ;  Arm- 
strong,  150,   152;     Blanksma,    151; 
Collie,  157 ;  Crum-Brown  andGibson, 
149;     Flurscheim,    153;    Fry,    160; 
Holleman,  151,  156;    Hubner,  149; 
Lapworth,     158;       Noelting,     149; 
Obermuller,    155;    Tschitschibabin, 
154 ;  Vorliinder,  150. 

—  of  double  bond,  74. 

—  of  free  valency,  77. 

—  of  reactions,  Erlenmeyer,  jun.,  145; 
Kekule,    110;     Lander,    127;     Lap- 
worth,  127;    Michael,  110,  113,  125; 
Nef,   110,    125;      van't   Hoff,    110; 
Vorlander,  147;    Williamson,    110; 
Wislicenus,  126. 

—  of  unsaturation,  74,  82. 

—  of  valency,   57,   83;      Abegg   and 
Bodlander,  58,    101;     Briggs,    102; 
Clayton, 58;  Flurscheim,  87;  Friend, 
95;      Stark,     100;      Thomson,    98; 
Tschitschibabin,    88;     Werner,   82; 
Wunderlich,  89. 

—  of  Baeyer,  76,    178;     Collie,   157; 
Flurscheim,    87;      Holleman,    156; 
Lapworth,  127,  158;    Michael,  114, 
191 ;    Thiele,  133 ;    Tschitschibabin, 
88;  Wislicenus,  126. 

ThiQ-aldehydes,  128. 

Thio-anilides,  215. 

Thio-indoxyl,  187. 

Thioketones-  128. 

Thujane,  164. 

Thujol,  167. 

Thymoquinone,  oxime  formation,  332. 

Thymolic  acid,  ester ificati on  of,  336. 

Tolane  trichloride,  65. 

Triacetyl  benzene,  226. 

Triazane  compounds,  256. 

Triazene  compounds,  256. 

Triazoles,  259. 

Tribenzoyl,  benzene,  226. 

Tribiphenylmethane,  61. 

Tribromobenzene,  202. 

Tribromobutane  dicarboxylic  acid,  182. 

Trimeric  acid,  227;  estcrificationof,  338. 

Trimethylacrylic  acid,  reactivity  of, 
353. 

Trimethylammonium-azobenzene  chlo- 
ride, 148. 

Trimethylbenzoic  acid,  esterification 
of,  334. 

Trimethyl  benzonitrile,  hydrolvsis  of, 
375. 


Trimethyleneiminc,  257. 
Triphenylmethane,      derivatives     of, 

195. 
Triphenylmethyl,  59,  60 ;    formula  of, 

64. 

—  chloride,  62. 
Trithio-aldehydes,  174. 
Trithioketones,  174. 
Truxillic  acid,  181. 
Turpentine  oil,  2. 
Types»of  reactions,  109. 

Types,  theory  of,  21,  44 ;  condensed, 
47 ;  mixed,  48. 

Unimolecular  non  reversible  reactions, 

277. 
Union  of  carbon-nitrogen,  254;  carboii' 

carbon,  174 ;  carbon-oxygen,  268. 
Unitary  system,  25. 
Unsaturated  acids,  reduction  of,  167. 

—  compounds,  reactions  of,  112. 

—  groups,  nature  of,  74. 
Urea,  synthesis  of,  9. 
Uric  acid,  2. 

Valency,  auxiliary,  and  principal,  90; 
carbon,  56;  contra  and  normal,  58, 
101;  double,  99;  electrons,  100; 
latent,  99 ;  isomerism,  92  ;  partial, 
133;  primary  and  secondary,  59; 
residual,  99 ;  variable.  57 ;  volume, 
84 ;  and  affinity,  107  ;  and  physical 
properties,  84. 

—  theories   of,    50,    83;     Abegg  and 
Bodlander,   101;     Briggs,  94,   102; 
Claus,  85;  Flurscheim,  87  ;    Friend, 
95;    Knoevenagel,  77;    Stark,   100; 
Thomson,  98  ;    Thorpe,  78  ;    Tschit- 
schibabin,   88;      Werner,    85,    90; 
Wunderlich,  89. 

—  theories    of,   electrochemical,    96; 
electronic,  97. 

Velocity  of  intramolecular  rearrange- 
ment, 278;  of  esterification,  290, 
335. 

—  of  organic  reactions,  275. 
Vinylacrylic  acid,  202. 
Vital  force,  3,  9. 

Xanthone,  274. 

Xylidines,  methylation  of,  376. 

Xyloquinone,  241. 

Zinc  alkyl  compounds,  205;  condensa- 
tions, 206. 


INDEX  OF  AUTHORS 


Abegg  and  Bodlander,  58,  101,  232. 
Angeli,  2C3. 

—  and  Marchetti,  234. 
Anschiitz,  350. 

—  and  Immendorff,  198. 
Armstrong,  benzene  substitution,  150, 

152. 

—  and  Caldwell,  289. 
Arrhenius,  99. 
Aschan,  180. 
Austin,  172. 
Auwers,  202,  203,  353. 
Avogadro,  3. 

Baeyer,  strain  theory,  76,  178;  syn- 
thesis of  cyclic  compounds,  225 ;  of 
cyclohexane,  185;  cf  diphenyl- 
methane,  243;  of  mesityloxide,  238; 
of  phorone,  238. 

—  and  Drewsen,  239. 

—  and  Villiger,  122,  148,  209. 
Baly,  101. 

Bamberger,  123,  141,  255,  348. 

—  and  Kising,  348. 
Barbier,  209. 
Barlow  and  Pope,  84. 
Bauer,  88,  116,  118. 

—  and  Baum,  333. 
Beckrnann  and  Paul,  247. 

—  and  Wegerhoff,  333. 
Bertagnini,  248. 
Berthelot,  273,  275. 

—  and  St.  Gilles,  276,  313. 
Berzelius,  13;  radical  of  ben  zoic  acid,  1; 

atomic  weights,  3  ;  electrochemical 
theory,  6,  83  ;  organic  compounds,  8 ; 
school  of,  31. 

Biltz,  118,  119. 

Bischoff,  350. 

—  and  Each,  191. 
Bladin,  267. 
Blaise,  210,  213. 
Blanc,  200. 
Blanksma,  151,  278. 
Blomstrand,  109. 
Bodroux,  212,  214. 
Boehm,  243. 
Bohr,  97. 
Bolseken,  297. 
Bone,  150. 

—  and  Sprankling,  192. 

—  and   Sudborough  and  Sprankling, 
342. 


Borschc,  138. 
Bouveault,  212. 
Bray  and  Branch,  104. 
Bredig,  162. 

—  and  Fraenckel,  291. 
Brest  and  Kallen,  205. 
Briggs,  94,  102. 
Briner,  92. 

Briihl,  70. 
Brunei,  165. 
Bruner,  283. 

—  and  Vorbrodt,  327. 
Buchner,  180. 

Buchner  and  Curt  ins,  204,  205. 
Bugarsky,  321. 
Bunsen,  12. 

—  and  Roscoe,  322. 
Burke  and  Donnan,  303. 
Busch,  315. 
Butlerow,  206. 

Cain  and  Nicoll,  293. 
Chattaway,  296. 

—  and  Wadmore,  70. 
Chevreul,  8. 

Claisen,  223,  234,  235,  238. 
Glaus,  85,  330,  331,  344. 
Clayton,  58. 
Cohen,  346. 

—  and  Dakin,  152. 

—  and  Dudley,  347. 

—  an  1  Hartley,  152. 

—  and  McCandlish,  350. 

—  and  Woodroffe  and  Anderson,  389. 
Collie,  157. 

Combes,  197. 

Conrad,  189,  192. 

Couper,  54. 

Crum-Brown  and  Gibson,  149. 

—  and  Walker,  200. 

Dakin,  172,  241. 
Dalton,  5. 

Davy,  H..  7,  24,  96,  171. 
Dawson,  291. 

—  and  Leslie,  318. 

—  and  Powis,  320. 

-  and  Wheatley,  319. 
Decker,  142,  347. 
Dehn  and  Dewey,  111. 
Demjanow,  184. 
Derlon,  200. 
Dieckmann,  226,  227. 


INDEX  OF  AUTHORS 


363 


Dimroth,  215,  216,  265. 
Dobereiner,  171. 
Dobner,  202. 
Donnan,  292. 

—  and  Potts,  303. 
Drude,  100. 
Dulong,  24. 

—  and  Petit,  3. 
Dumas,  5,  17,  21. 

—  and  Boullay,  10. 
Dunstan  and  Bossi,  70. 

Effront,  346. 
E inborn  and  Diehl,  239. 
Engler  and  Weissberg,  122. 
Ephraim,  105, 
Erlenmeyer,  jun.,  145,  234. 

Fa  Ik,  99. 
Faraday,  6. 
Fawcett,  316. 
Feist,  73. 
Fenton,  172. 
Fischer.  E.,  345. 

—  and  Brieger,  83. 

—  and  Dilthey,  344. 

—  and  Giebe,  343. 

—  and  Windaus,  346. 
Fittig,  246,  247,  248. 

—  and  Daimler,  217. 

—  and  Jayne,  250. 
Fleischauer,  234. 
FJiirscheim,  87,  153. 
Fokin,  163. 

Frankland,  early  researches,  83; 
valency,  50  ;  zinc  alkyl  compounds, 
188,  205. 

—  and  Duppa,  206,  221. 
Freer,  247. 

Freund,  185.  189,  206. 
Friedel  and  Crafts,  195. 

—  and  Ladenburg,  205. 
Friedlander,  346. 
Friend,  95,  99. 
Fritzsche,  324. 

Fry,  99,  160. 

Gabriel,  242. 
Gattermann,  212,  334. 

—  and  Koch,  196. 
Gay-Lussac,  3,  10,  12. 
Geuther,  220,  273. 
Geuther  and  Hubner,  241. 
Gmelin,  6. 
Goldschmidt,  128,  290,  335. 

—  and  Bachs,  290. 

—  and  Lawson,  199. 

—  and  Merz.  295. 

—  and  Reinders,  287. 

—  and  Sunde,  290. 

—  and  Udby,  290. 

—  and  Wachs,  290. 
Gomberg,  60. 


Gomberg  and  Cone,  64. 

Graham,  23. 

Grignard,  208. 

Guldberg  and  Waage,  276. 

Gustavson,  198. 

Gyr,  341. 

Haller,  342. 

—  and  Bauer,  190. 
Hann  and  Lapworth,  245. 
Hantzsch,  64,  333 ;  action  of  chlorine 

on  phenols,  183 ;    decomposition  of 
diazo-compounds,  293. 

—  and  Vogt,  267. 
Harries,  120,  135. 

—  and  Hubner,  333. 
Harrow,  191. 
Hartley,  88. 

Hausser  and  Miiller,  293. 

Heller  and  Schiilke,  197. 

Helinholtz,  96. 

Hennel,  9,  43. 

Henrich,  190. 

Henry,  83,  243,  311. 

Hibbert  and  Sudborough,  210. 

Hinrichsen,  56,  76,  77,  109,  143. 

Hirst  and  Cohen. 

Hofer,  201. 

Hofinann,  32,  70,  171,  330. 

—  and  Bugge,  68. 
Holleman,  151,  152,  156,  305. 
Houben,  213,  214. 
Howard,  71. 

Hubner,  149. 
Hudson,  310. 

Ipatiew,  164,  168. 

Jacobsen,  198. 
Jacobson,  64,  330. 
Jannasch  and  Weiler. 
Japp,  240. 

—  and  Streatfeild,  241. 

Kane,  247. 
Kannonikow,  207. 
Kehrmann,  62,  332. 
Kehrmann  and  Wentzel,  147. 
Kekule,  71,  110;    theory  of  atomicity, 

49 ;    of  valency,  50 ;    quadrivalence 

of  carbon,  52. 
Kellas,  335,  337,  343. 
Kempf,  172. 
Kenner,  180. 
Kipping,  197,  255. 

—  and  Hall,  197. 

—  and  Perkin,  238,  247. 

—  and  Sahvay,  123. 
Kistiakowsky,  312. 
Klages,  116. 
Klein,  70. 
Knoblauch,  313. 


364 


INDEX  OF  AUTHORS 


Knoevenagel,  77,  90,  204,  241. 

Knorr,  262. 

Koehl  and  Dintner,  144. 

Koenigs  and  Happe,  243. 

Kohler,  137,  215. 

Konigs,  849. 

Kolbe,  58. 

Komppa,  227. 

Kopp,  85. 

KOtz,  180. 

Kunckelland  Hildebrandt,  353. 

Kuster  and  Stallberg,  345. 

Lander,  125,  127. 

Lapworth,  acetoacetic  ester  condensa- 
tion, 127,  218,  232  ;  substitution  in 
benzene,  158;  addition  of  hydrogen 
cyanide,  205  ;  benzoin  condensation, 
246 ;  action  of  halogens  on  carbonyl 
compounds,  318. 

Lapworth  and  Fitzgerald,  291. 

—  and  Partington,  291. 

Lawrence,  218. 

Le  Bas,  84. 

Lescoeur  and  Kigaut,  70. 

Lewis,  104. 

Lichty,  341. 

Liebig  and  Wohler,  245. 

Lipp  and  Kichard,  243. 

Liwow,  205. 

L5b,  65. 

Locke  and  Edwards,  94. 

Lossen,  76. 

Low,  163,  171. 

Lowry,  308,  310. 

—  and  Magson,  309. 
Luther  and  Weigert,  323,  324. 

Malaguti,  276. 
Manasse,  243. 
Marckwald,  242,  258. 

—  and  McKenzie,  339. 
Markownikoff,  114,  179,  186. 
Marshall  and  Perkin,  238. 
McKenzie,  209,  339. 
Meisenheimer,  148. 
Mellor,  199,  329. 
Menschutkin,  199,  341. 
Merz,  330. 

Meyer,  K.  H.,  64. 

—  and  Lenhardt,  139. 
Meyer,  V.,  195,  333,  334,  353. 

—  and  Lecco,  358. 

—  and  Saam,  329. 

Michael,  polymerisation,  60;  plasticity, 
108;  chemical  neutralisation,  113; 
addition  of  halogens,  118;  hetero- 
geneous addition,  124 ;  on  Thiele's 
theory,  143;  acetoacetic  ester  re- 
actions, 190 ;  additive  reactions,  202 ; 
acetoacetic  ester  formation,  230 ; 
Perkin  reaction,  249,  250;  steric 
hindrance,  340. 


Michael  and  Hibbert,  70. 
v.  Miller,  201. 

—  and  Hofer,  201. 
Mitscherlich,  3,  5,  15. 
Moissan  and  Moureu,  202. 
Montemartini,  200. 
Moseley,  97. 

Moureu  and  Mignonac,  132. 
Miiller,  203. 

Nef,  acetoacetic  ester,  229 ;  additive 
process,  110,  112,  113,  125  ;  benzoin 
condensation,  245 ;  structure  of  acety- 
lene, 73  ;  fulminic  acid,  71  ;  hydro- 
gen cyanide,  69;  isocyanides,  66; 
metallic  cyanides,  70. 

Nernst,  323. 

Nietzki  and  Schneider,  332. 

Noelting,  149,  349. 

Noyes,  99,  203. 

—  and  Cottle,  281. 

Obermiller,  154. 

Oddo,  214. 

Olivier  and  Boseken,  199. 

Oppenheim  and  Precht,  220. 

Orndorff  and  Cameron,  324. 

Orton  and  King.  279. 

—  and  Jones,  279. 
Ostwald,  113. 

Paal,  162. 

—  and  Kromschrbder,  347. 
Palazzo  and  Marogna,  268. 
Pasteur,  6. 

Patterson  and  Montgomerie,  327. 

v.  Pechmann,  70;    hexane  derivatives, 

190  ;  isotriazoles,  272 ;  pyrrole,  204  ; 

quinories,  240. 
Peligot,  12. 

Peratoner  and  Palazzo,  70. 
Perkin,  W.  H.,  sen.,  248. 

—  jun.,  synthesis  of  carnphoronic  acid, 
219  ;    of  isocamphoronic  acid,   203, 
353;    of  cyclic  compounds,  181,  185, 
192  ;  of  cyclohexane,  109  ;  of  w-toluic 
acid,  202. 

—  and  Goldsworthy,  180. 

—  and  Haworth,  242. 

— -  and  Simonsen,  180,  182. 

Perrier,  297. 

Petrenko-Kritschenko,  128. 

Pfeiffer,  199. 

Piccard,  64. 

Piloty,  243. 

Pinner,  331. 

Piutti,  227. 

Posner,  144. 

Pschorr  and  Hoppe,  255. 

Ram  berg,  68. 
Ramsay,  99. 
Raper,  238. 


INDEX  OF  AUTHORS 


365 


Keboul,  115. 

Reformatsky,  217. 

Regnault,  15. 

Reicher,  844. 

Reimer  and  Tiemann,  195. 

Remsen  and  Reid,  331,  345. 

Richards,  55. 

Riedel  and  Schulz,  144. 

Rivett  and  Sidgwick,  135. 

Robinson  and  Hamilton,  142. 

Rosanoff,  185. 

—  Clark  and  Sibley,  289. 
Rose,  270. 

Rosenheim  and  Singer,  214. 
Ruff,  172. 
Ruhemann,  255. 

—  and  Cunningham,  202. 
Runge,  15. 
Rutherford,  97. 

Sabatier  and  Mailhe,  170. 

—  and  Murat,  170. 

—  and  Senderens,  164. 
Sachs  and  Loevy,  212,  215. 
Saytzeff,  115,  206. 
Scheele,  2,  9. 

Schlenk,  60,  61,  65,  247. 

Schlotterbeck,  204. 

Schlundt,  70. 

Schmidlin,  60,  61. 

--  and  Lang,  110. 

Schmidt,  119,  209,  238. 

Scholl,  72,  196. 

Scholtz  and  Wassermann,  346. 

Schonbein,  121. 

Schraube,  111. 

Schroeder,  85. 

Serturner,  8. 

Sidgwick,  69. 

Simon,  243. 

Skita,  163. 

Slator,  199. 

Smith,  333. 

Spiegel,  99. 

Stange,  1. 

Staudinger,  129. 

Steele,  198,  297. 

Stewart,  128,251. 

Stobbe,  242. 

Stohmann  and  Kleber,  181 

Straus,  133. 

Strecker,  249. 

Sudborough,  331,  341. 

—  and  Feilmann,  344. 

—  and  Jackson,  345. 

—  and  Lloyd,  290,  292,  342,  345. 

—  and  Roberts,  342. 

—  and  Thomas,  117. 
Swientoslawsky,  88. 

Tauret,  310. 
Taylor,  247. 
Thiele,  133,  256,  267. 


Thiele'and  Meisenheimer,  145. 
Thomsen,  75,  113,  134. 
Thomson,  97,  98. 
Thorpe,  J.  F.  190,  252. 

—  and  Beesley  and  Ingold,  183. 

—  and  Bland,  79. 

—  and  Campbell,  182. 

—  and  Rogerson,  78. 

—  and  Thole,  78. 

—  and  Wood,  81. 
Tiemann  and  Kriiger,  239. 

—  and  Schmidt,  240. 
Tilden,  119. 
Traube,  M.,  122. 

—  I.,  84. 
Tschelinzeff,  217. 
Tschitschibabin,  88,  154,  214. 
Tschugaeff,  164. 

Tubandt,  327. 

—  and  Mohr,  291. 
Turner,  96. 

Ullmann,  188,  199. 
Urech,  310. 

Van  den  Brock,  97. 

Van't  Hoff,  evidence  of  stereo- 
chemistry, 75  ;  double  bond,  75 ; 
inertia  of  carbon,  108;  order  of  re- 
actions, 282,  283;  solvent  and 
reaction  velocity,  328 ;  types  of  re- 
actions, 109. 

—  and  Cohen,  329. 
Veraguth,  186. 
Volhard,  234. 

Vorlander.  additive  power  of  CO-group, 
128;  additive  process,  147 ;  rule  of 
substitution,  150  ;  Friedel-Crafts  re- 
action, 195  ;  synthesis  of  cyclic  com- 
pounds, 203,  226. 

Wade,  68. 
Wagner,  206. 
Walker,  E.  E.,  296. 
Walker,  J.,  201. 

—  and  Appleyard,  313. 

—  and  Hambly,  295. 

—  and  Kay,  296. 

Walker,  J.  W.,  and  Spencer,  198. 
Wallach,  162,  184,  219,  255. 
Wegscheider,  299,  339,  842. 
Weigert,  323. 
Wenzel,  275. 

Werner,  theory  of  valency,  60,  85,  90 ; 
theory  of  unsaturation,  82. 

—  and  Zilkens,  210. 
Werth,  330. 
Whiddington,  98. 
Wieland,  65,  72,  119,  215.      . 

—  and  Bloch,  119. 
Wilhelmy,  276. 
Williamson,  41,  46,  48,  110. 


866 


INDEX  OF  AUTHORS 


Willstiitter,  cycloparaffins,  185,  225;  re- 
duction  with  colloidal  platinum,  163. 

—  and  Veraguth,  186. 
Wilsmore,  129. 

Wislicenus,  J.,  acetoacetic  ester,  222 ; 
synthesis  of  acids,  185,  188 ;  cyclic 
ketones,  189,  200  ;  cyclopentane,  185. 

Wislicenus,  W.,  126,  226,  227,  234. 

Wohl  and  Schiff,  257. 

—  and  Schweitzer,  201. 
Wohler,  9. 
Wollaston,  6. 


Wreden,  183. 
Wunderlich,  39. 

Wurtz,  amines,  45  ;    glycols,  47  ;    syn- 
thetic methods,  188,  237. 


Zeise,  10,  15. 

Zelinsky,  184,  185,  186.  217. 

—  and  Gutt,  219. 

—  and  Moser,  211. 
Zerewitinoff,  210. 
Zincke,  183. 


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DEC   18  1938 

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UNIVERSITY  OF  CALIFORNIA  LIBRARY 


